diff --git a/DESCRIPTION b/DESCRIPTION index 16acdfb..5d017d7 100644 --- a/DESCRIPTION +++ b/DESCRIPTION @@ -1,7 +1,7 @@ Package: curatedCRCData Type: Package Title: Colorectal Cancer Gene Expression Analysis -Version: 2.45.4 +Version: 2.45.5 Date: 2026-10-03 Authors@R: c( person("Princy", "Parsana", role = "aut"), @@ -39,8 +39,12 @@ VignetteBuilder: knitr License: Artistic-2.0 biocViews: ExperimentData, + ExpressionData, CancerData, - ExpressionData + ColonCancerData, + MicroarrayData, + RNASeqData, + GEO URL: https://github.com/waldronlab/curatedCRCData BugReports: https://github.com/waldronlab/curatedCRCData/issues BuildResaveData: no diff --git a/NEWS.md b/NEWS.md index bf00827..7519499 100644 --- a/NEWS.md +++ b/NEWS.md @@ -31,6 +31,15 @@ * Removed `external_data_store.txt` and `Namespace: auto`; explicit NAMESPACE exporting only `curatedCRCData()`. +## DOCUMENTATION AND METADATA + +* Repaired UTF-8 transcoding damage ("??" artifacts) in 32 dataset man + pages: author names, journal references, and statistical symbols + restored (ASCII equivalents). +* biocViews extended to ColonCancerData, MicroarrayData, RNASeqData, and + GEO for better discoverability. +* Removed the empty FULLVcuratedCRCData_counts.csv placeholder. + # curatedCRCData 2.43.1 * Updated package maintainer to Levi Waldron (). diff --git a/inst/extdata/FULLVcuratedCRCData_counts.csv b/inst/extdata/FULLVcuratedCRCData_counts.csv deleted file mode 100755 index e16c76d..0000000 --- a/inst/extdata/FULLVcuratedCRCData_counts.csv +++ /dev/null @@ -1 +0,0 @@ -"" diff --git a/man/GSE11237_eset.Rd b/man/GSE11237_eset.Rd index 423e58d..ef6e157 100644 --- a/man/GSE11237_eset.Rd +++ b/man/GSE11237_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Auman JT, Church R, Lee SY, Watson MA, Fleshman JW, Mcleod HL.??Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation.??Eur J Cancer??2008 Aug + Experimenter name: Auman JT, Church R, Lee SY, Watson MA, Fleshman JW, Mcleod HL. Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation. Eur J Cancer 2008 Aug Laboratory: Auman, Mcleod 2008 Contact information: Title: Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation. diff --git a/man/GSE12225.GPL3676_eset.Rd b/man/GSE12225.GPL3676_eset.Rd index 5665ffd..b8fa0fa 100644 --- a/man/GSE12225.GPL3676_eset.Rd +++ b/man/GSE12225.GPL3676_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Lips EH, van Eijk R, de Graaf EJ, Oosting J et al.??Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis.BMC Cancer??2008 Oct 29 + Experimenter name: Lips EH, van Eijk R, de Graaf EJ, Oosting J et al. Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis. BMC Cancer 2008 Oct 29 Laboratory: Lips, Morreau 2008 Contact information: Title: Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis. diff --git a/man/GSE12945_eset.Rd b/man/GSE12945_eset.Rd index 2a1e8ef..73adef9 100644 --- a/man/GSE12945_eset.Rd +++ b/man/GSE12945_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Staub E, Groene J, Heinze M, Mennerich D et al.??An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types.??J Mol Med (Berl)??2009 Jun + Experimenter name: Staub E, Groene J, Heinze M, Mennerich D et al. An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types. J Mol Med (Berl) 2009 Jun Laboratory: Staub, Rosenthal 2009 Contact information: Title: An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types. diff --git a/man/GSE13067_eset.Rd b/man/GSE13067_eset.Rd index 8fef99b..3a29dc8 100644 --- a/man/GSE13067_eset.Rd +++ b/man/GSE13067_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Jorissen RN, Lipton L, Gibbs P, Chapman M et al.??DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers.??Clin Cancer Res??2008 Dec 15 + Experimenter name: Jorissen RN, Lipton L, Gibbs P, Chapman M et al. DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers. Clin Cancer Res 2008 Dec 15 Laboratory: Jorissen and Sieber 2008 Contact information: Title: DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers. diff --git a/man/GSE14095_eset.Rd b/man/GSE14095_eset.Rd index 5111a9e..7945809 100644 --- a/man/GSE14095_eset.Rd +++ b/man/GSE14095_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Watanabe T, Kobunai T, Yamamoto Y, Matsuda K et al.??Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients.??Clin Transl Oncol??2011 Jun + Experimenter name: Watanabe T, Kobunai T, Yamamoto Y, Matsuda K et al. Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients. Clin Transl Oncol 2011 Jun Laboratory: Watanabe, Hashimoto 2008 Contact information: Title: Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients. diff --git a/man/GSE14333_eset.Rd b/man/GSE14333_eset.Rd index 27daf6b..8fb6bb8 100644 --- a/man/GSE14333_eset.Rd +++ b/man/GSE14333_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Jorissen RN, Gibbs P, Christie M, Prakash S et al.??Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer.??Clin Cancer Res??2009 Dec 15 + Experimenter name: Jorissen RN, Gibbs P, Christie M, Prakash S et al. Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer. Clin Cancer Res 2009 Dec 15 Laboratory: Jorissen and Sieber 2008 Contact information: Title: Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer. diff --git a/man/GSE16125.GPL5175_eset.Rd b/man/GSE16125.GPL5175_eset.Rd index 280e92a..d2ed9c0 100644 --- a/man/GSE16125.GPL5175_eset.Rd +++ b/man/GSE16125.GPL5175_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Reid JF, Gariboldi M, Sokolova V, Capobianco P et al.??Integrative approach for prioritizing cancer genes in sporadic colon cancer.??Genes Chromosomes Cancer??2009 Nov + Experimenter name: Reid JF, Gariboldi M, Sokolova V, Capobianco P et al. Integrative approach for prioritizing cancer genes in sporadic colon cancer. Genes Chromosomes Cancer 2009 Nov Laboratory: Reid, Pierotti 2009 Contact information: Title: Integrative approach for prioritizing cancer genes in sporadic colon cancer. diff --git a/man/GSE17536_eset.Rd b/man/GSE17536_eset.Rd index 77114c7..2926525 100644 --- a/man/GSE17536_eset.Rd +++ b/man/GSE17536_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Smith JJ, Deane NG, Wu F, Merchant NB et al.??Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.??Gastroenterology??2010 Mar - Laboratory: Smith JJ,??Beauchamp RD 2009 + Experimenter name: Smith JJ, Deane NG, Wu F, Merchant NB et al. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology 2010 Mar + Laboratory: Smith JJ, Beauchamp RD 2009 Contact information: Title: Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. URL: diff --git a/man/GSE17537_eset.Rd b/man/GSE17537_eset.Rd index d7ffba0..19d615b 100644 --- a/man/GSE17537_eset.Rd +++ b/man/GSE17537_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Smith JJ, Deane NG, Wu F, Merchant NB et al.??Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.??Gastroenterology??2010 Mar - Laboratory: Smith JJ,??Beauchamp RD 2009 + Experimenter name: Smith JJ, Deane NG, Wu F, Merchant NB et al. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology 2010 Mar + Laboratory: Smith JJ, Beauchamp RD 2009 Contact information: Title: Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. URL: diff --git a/man/GSE17538.GPL570_eset.Rd b/man/GSE17538.GPL570_eset.Rd index 68440ab..a75d65e 100644 --- a/man/GSE17538.GPL570_eset.Rd +++ b/man/GSE17538.GPL570_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Smith JJ, Deane NG, Wu F, Merchant NB et al.??Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.??Gastroenterology??2010 Mar - Laboratory: Smith JJ,??Beauchamp RD 2009 + Experimenter name: Smith JJ, Deane NG, Wu F, Merchant NB et al. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology 2010 Mar + Laboratory: Smith JJ, Beauchamp RD 2009 Contact information: Title: Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. URL: diff --git a/man/GSE18105_eset.Rd b/man/GSE18105_eset.Rd index 1ad2c6b..90d549d 100644 --- a/man/GSE18105_eset.Rd +++ b/man/GSE18105_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Matsuyama T, Ishikawa T, Mogushi K, Yoshida T et al.??MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer.??Int J Cancer??2010 Nov 15 + Experimenter name: Matsuyama T, Ishikawa T, Mogushi K, Yoshida T et al. MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer. Int J Cancer 2010 Nov 15 Laboratory: Matsuyama, Sugihara 2009 Contact information: Title: MUC12 mRNA expression is an independent marker of prognosis in stage II and stage III colorectal cancer. diff --git a/man/GSE21510_eset.Rd b/man/GSE21510_eset.Rd index f11a8f3..a67e984 100644 --- a/man/GSE21510_eset.Rd +++ b/man/GSE21510_eset.Rd @@ -2,13 +2,13 @@ \alias{ GSE21510_eset } \docType{data} \title{ Clinical significance of osteoprotegerin expression in human colorectal cancer. } -\description{ This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. The mRNA expression of candidate genes was investigated by quantitative reverse transcriptase PCR (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 274 CRC patients.Using microarray analysis, we identified 6 candidate genes related to distant metastases in CRC patients. Among these genes, osteoprotegerin (OPG) is known to be associated with aggressiveness in several cancers through inhibition of apoptosis via neutralization of the function of TNF-related apoptosis-inducing ligand. The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastases than those without metastases. Overexpression of OPG protein was associated with significantly worse overall survival and relapse-free survival. Moreover, overexpression of the OPG protein was an independent risk factor for CRC recurrence.Overexpression of OPG may be a predictive biomarker of CRC recurrence and a target for treatment of this disease.??2011 AACR. } +\description{ This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. The mRNA expression of candidate genes was investigated by quantitative reverse transcriptase PCR (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 274 CRC patients.Using microarray analysis, we identified 6 candidate genes related to distant metastases in CRC patients. Among these genes, osteoprotegerin (OPG) is known to be associated with aggressiveness in several cancers through inhibition of apoptosis via neutralization of the function of TNF-related apoptosis-inducing ligand. The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastases than those without metastases. Overexpression of OPG protein was associated with significantly worse overall survival and relapse-free survival. Moreover, overexpression of the OPG protein was an independent risk factor for CRC recurrence.Overexpression of OPG may be a predictive biomarker of CRC recurrence and a target for treatment of this disease. (c) 2011 AACR. } \usage{data( GSE21510_eset )} \format{ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Tsukamoto S, Ishikawa T, Iida S, Ishiguro M et al.??Clinical significance of osteoprotegerin expression in human colorectal cancer.??Clin Cancer Res2011 Apr 15 + Experimenter name: Tsukamoto S, Ishikawa T, Iida S, Ishiguro M et al. Clinical significance of osteoprotegerin expression in human colorectal cancer. Clin Cancer Res 2011 Apr 15 Laboratory: Tsukamoto, Sugihara 2010 Contact information: Title: Clinical significance of osteoprotegerin expression in human colorectal cancer. diff --git a/man/GSE21815_eset.Rd b/man/GSE21815_eset.Rd index bfa644d..d5294e1 100644 --- a/man/GSE21815_eset.Rd +++ b/man/GSE21815_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Kogo R, Shimamura T, Mimori K, Kawahara K et al.??Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers.??Cancer Res??2011 Oct 15 - Laboratory: Mori M,??Mimori K,??Yokobori T 2010 + Experimenter name: Kogo R, Shimamura T, Mimori K, Kawahara K et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 2011 Oct 15 + Laboratory: Mori M, Mimori K, Yokobori T 2010 Contact information: Title: Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. URL: diff --git a/man/GSE24549.GPL5175_eset.Rd b/man/GSE24549.GPL5175_eset.Rd index 35731b8..623d921 100644 --- a/man/GSE24549.GPL5175_eset.Rd +++ b/man/GSE24549.GPL5175_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Sveen A,????esen TH,??Rognum TO,??Lothe RA,??Skotheim RI. Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival. Genome Med 2011 May 27 - Laboratory: Sveen A,????esen TH,??Rognum TO,??Lothe RA,??Skotheim RI 2011 + Experimenter name: Sveen A, Agesen TH, Rognum TO, Lothe RA, Skotheim RI. Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival. Genome Med 2011 May 27 + Laboratory: Sveen A, Agesen TH, Rognum TO, Lothe RA, Skotheim RI 2011 Contact information: Title: Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival. URL: diff --git a/man/GSE24550.GPL5175_eset.Rd b/man/GSE24550.GPL5175_eset.Rd index 6baa36b..4bc740d 100644 --- a/man/GSE24550.GPL5175_eset.Rd +++ b/man/GSE24550.GPL5175_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Sveen A, Agesen TH, Nesbakken A, Rognum TO et al.??Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival.Genome Med??2011 May 27 - Laboratory: Sveen A,????esen TH,??Rognum TO,??Lothe RA,??Skotheim RI 2011 + Experimenter name: Sveen A, Agesen TH, Nesbakken A, Rognum TO et al. Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival. Genome Med 2011 May 27 + Laboratory: Sveen A, Agesen TH, Rognum TO, Lothe RA, Skotheim RI 2011 Contact information: Title: Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival. URL: diff --git a/man/GSE2630_eset.Rd b/man/GSE2630_eset.Rd index f7a182b..0606110 100644 --- a/man/GSE2630_eset.Rd +++ b/man/GSE2630_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Bandr??E,??Malumbres R,??Cubedo E,??Sola J,??Garc??Foncillas J,??Labarga A. A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients. Oncol Rep 2007 May - Laboratory: Bandr??E,??Malumbres R,??Cubedo E,??Sola J,??Garc??Foncillas J,??Labarga A 2005 + Experimenter name: Bandres E, Malumbres R, Cubedo E, Sola J, Garcia-Foncillas J, Labarga A. A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients. Oncol Rep 2007 May + Laboratory: Bandres E, Malumbres R, Cubedo E, Sola J, Garcia-Foncillas J, Labarga A 2005 Contact information: Title: A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients. URL: diff --git a/man/GSE26682.GPL570_eset.Rd b/man/GSE26682.GPL570_eset.Rd index e91985b..0988b0d 100644 --- a/man/GSE26682.GPL570_eset.Rd +++ b/man/GSE26682.GPL570_eset.Rd @@ -2,14 +2,14 @@ \alias{ GSE26682.GPL570_eset } \docType{data} \title{ MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. } -\description{ Microsatellite instability (MSI) is displayed by approximately 15\% of colorectal cancers (CRC). Defective DNA mismatch repair generates mutations at repetitive DNA sequences such as those located in the double strand break (DSB) repair gene MRE11. We assessed the mutational status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors and found a strong correlation with MSI status in both cell lines and tumors. Therefore, we hypothesized that deficiency in MRE11 may sensitize CRC cells to poly(ADP-ribose) polymerase (PARP-1) inhibition based on the concept of synthetic lethality. We further assessed the activity of the PARP-1 inhibitor, ABT-888, in CRC cell lines and observed preferential cytotoxicity in those MSI cell lines harboring mutations in MRE11 compared with both wild-type cell lines and microsatellite stable (MSS) cell lines. A significant correlation between MRE11 expression levels and cytotoxicity to ABT-888 at 10 ??M was observed (R?? = 0.915, P < 0.001). Using two experimental approaches, including short hairpin RNA knocking down MRE11 in the wild-type and MSS cell line SW-480 and a second cell line model transfected with mutant MRE11, we experimentally tried to confirm the role of MRE11 in conferring sensitivity to PARP-1 inhibition. Both models led to changes in proliferation in response to ABT-888 at different concentrations, and a drug-response effect was not observed, suggesting a possible contribution of additional genes. We conclude that MSI colorectal tumors deficient in DSB repair secondary to mutation in MRE11 show a higher sensitivity to PARP-1 inhibition. Further clinical investigation of PARP-1 inhibitors is warranted in MSI CRCs. } +\description{ Microsatellite instability (MSI) is displayed by approximately 15\% of colorectal cancers (CRC). Defective DNA mismatch repair generates mutations at repetitive DNA sequences such as those located in the double strand break (DSB) repair gene MRE11. We assessed the mutational status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors and found a strong correlation with MSI status in both cell lines and tumors. Therefore, we hypothesized that deficiency in MRE11 may sensitize CRC cells to poly(ADP-ribose) polymerase (PARP-1) inhibition based on the concept of synthetic lethality. We further assessed the activity of the PARP-1 inhibitor, ABT-888, in CRC cell lines and observed preferential cytotoxicity in those MSI cell lines harboring mutations in MRE11 compared with both wild-type cell lines and microsatellite stable (MSS) cell lines. A significant correlation between MRE11 expression levels and cytotoxicity to ABT-888 at 10 uM was observed (R^2 = 0.915, P < 0.001). Using two experimental approaches, including short hairpin RNA knocking down MRE11 in the wild-type and MSS cell line SW-480 and a second cell line model transfected with mutant MRE11, we experimentally tried to confirm the role of MRE11 in conferring sensitivity to PARP-1 inhibition. Both models led to changes in proliferation in response to ABT-888 at different concentrations, and a drug-response effect was not observed, suggesting a possible contribution of additional genes. We conclude that MSI colorectal tumors deficient in DSB repair secondary to mutation in MRE11 show a higher sensitivity to PARP-1 inhibition. Further clinical investigation of PARP-1 inhibitors is warranted in MSI CRCs. } \usage{data( GSE26682.GPL570_eset )} \format{ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Vilar E,??Gruber SB,??Rennert G,??Bartnik CM,??Stenzel SL,??Iniesta MD,??Raskin L,Mukherjee B,??Ahn J,??Moreno V,??Morgan MA. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res 2011 Apr 1 - Laboratory: Vilar E,??Morgan MA 2011 + Experimenter name: Vilar E, Gruber SB, Rennert G, Bartnik CM, Stenzel SL, Iniesta MD, Raskin L, Mukherjee B, Ahn J, Moreno V, Morgan MA. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res 2011 Apr 1 + Laboratory: Vilar E, Morgan MA 2011 Contact information: Title: MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. URL: diff --git a/man/GSE26682.GPL96_eset.Rd b/man/GSE26682.GPL96_eset.Rd index 44fa200..cd35a8b 100644 --- a/man/GSE26682.GPL96_eset.Rd +++ b/man/GSE26682.GPL96_eset.Rd @@ -2,14 +2,14 @@ \alias{ GSE26682.GPL96_eset } \docType{data} \title{ MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. } -\description{ Microsatellite instability (MSI) is displayed by approximately 15\% of colorectal cancers (CRC). Defective DNA mismatch repair generates mutations at repetitive DNA sequences such as those located in the double strand break (DSB) repair gene MRE11. We assessed the mutational status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors and found a strong correlation with MSI status in both cell lines and tumors. Therefore, we hypothesized that deficiency in MRE11 may sensitize CRC cells to poly(ADP-ribose) polymerase (PARP-1) inhibition based on the concept of synthetic lethality. We further assessed the activity of the PARP-1 inhibitor, ABT-888, in CRC cell lines and observed preferential cytotoxicity in those MSI cell lines harboring mutations in MRE11 compared with both wild-type cell lines and microsatellite stable (MSS) cell lines. A significant correlation between MRE11 expression levels and cytotoxicity to ABT-888 at 10 ??M was observed (R?? = 0.915, P < 0.001). Using two experimental approaches, including short hairpin RNA knocking down MRE11 in the wild-type and MSS cell line SW-480 and a second cell line model transfected with mutant MRE11, we experimentally tried to confirm the role of MRE11 in conferring sensitivity to PARP-1 inhibition. Both models led to changes in proliferation in response to ABT-888 at different concentrations, and a drug-response effect was not observed, suggesting a possible contribution of additional genes. We conclude that MSI colorectal tumors deficient in DSB repair secondary to mutation in MRE11 show a higher sensitivity to PARP-1 inhibition. Further clinical investigation of PARP-1 inhibitors is warranted in MSI CRCs. } +\description{ Microsatellite instability (MSI) is displayed by approximately 15\% of colorectal cancers (CRC). Defective DNA mismatch repair generates mutations at repetitive DNA sequences such as those located in the double strand break (DSB) repair gene MRE11. We assessed the mutational status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors and found a strong correlation with MSI status in both cell lines and tumors. Therefore, we hypothesized that deficiency in MRE11 may sensitize CRC cells to poly(ADP-ribose) polymerase (PARP-1) inhibition based on the concept of synthetic lethality. We further assessed the activity of the PARP-1 inhibitor, ABT-888, in CRC cell lines and observed preferential cytotoxicity in those MSI cell lines harboring mutations in MRE11 compared with both wild-type cell lines and microsatellite stable (MSS) cell lines. A significant correlation between MRE11 expression levels and cytotoxicity to ABT-888 at 10 uM was observed (R^2 = 0.915, P < 0.001). Using two experimental approaches, including short hairpin RNA knocking down MRE11 in the wild-type and MSS cell line SW-480 and a second cell line model transfected with mutant MRE11, we experimentally tried to confirm the role of MRE11 in conferring sensitivity to PARP-1 inhibition. Both models led to changes in proliferation in response to ABT-888 at different concentrations, and a drug-response effect was not observed, suggesting a possible contribution of additional genes. We conclude that MSI colorectal tumors deficient in DSB repair secondary to mutation in MRE11 show a higher sensitivity to PARP-1 inhibition. Further clinical investigation of PARP-1 inhibitors is warranted in MSI CRCs. } \usage{data( GSE26682.GPL96_eset )} \format{ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Vilar E,??Gruber SB,??Rennert G,??Bartnik CM,??Stenzel SL,??Iniesta MD,??Raskin L,Mukherjee B,??Ahn J,??Moreno V,??Morgan MA. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res 2011 Apr 1 - Laboratory: Vilar E,??Morgan MA 2011 + Experimenter name: Vilar E, Gruber SB, Rennert G, Bartnik CM, Stenzel SL, Iniesta MD, Raskin L, Mukherjee B, Ahn J, Moreno V, Morgan MA. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res 2011 Apr 1 + Laboratory: Vilar E, Morgan MA 2011 Contact information: Title: MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. URL: diff --git a/man/GSE26906_eset.Rd b/man/GSE26906_eset.Rd index d8616e5..8d93d83 100644 --- a/man/GSE26906_eset.Rd +++ b/man/GSE26906_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Birnbaum DJ, Laibe S, Ferrari A, Lagarde A et al.??Expression Profiles in Stage II Colon Cancer According to APC Gene Status.??Transl Oncol??2012 Apr + Experimenter name: Birnbaum DJ, Laibe S, Ferrari A, Lagarde A et al. Expression Profiles in Stage II Colon Cancer According to APC Gene Status. Transl Oncol 2012 Apr Laboratory: Olschwang S 2011 Contact information: Title: Expression Profiles in Stage II Colon Cancer According to APC Gene Status. diff --git a/man/GSE27544_eset.Rd b/man/GSE27544_eset.Rd index 7f4e3d3..407be39 100644 --- a/man/GSE27544_eset.Rd +++ b/man/GSE27544_eset.Rd @@ -2,14 +2,14 @@ \alias{ GSE27544_eset } \docType{data} \title{ Genome-wide profiling characterizes CRCs with genetic instability and specific routes to HLA class I loss and immunoescape } -\description{ Bernal M,??Garc??Alcalde F,??Concha ????Blanco A,??Garrido F,??Ruiz-Cabello F } +\description{ Bernal M, Garcia-Alcalde F, Concha A, Blanco A, Garrido F, Ruiz-Cabello F } \usage{data( GSE27544_eset )} \format{ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Bernal M,??Garc??Alcalde F,??Concha ????Blanco A,??Garrido F,??Ruiz-Cabello F - Laboratory: Bernal M,??Garc??Alcalde F,??Concha ????Blanco A,??Garrido F,??Ruiz-Cabello F 2011 + Experimenter name: Bernal M, Garcia-Alcalde F, Concha A, Blanco A, Garrido F, Ruiz-Cabello F + Laboratory: Bernal M, Garcia-Alcalde F, Concha A, Blanco A, Garrido F, Ruiz-Cabello F 2011 Contact information: Title: Genome-wide profiling characterizes CRCs with genetic instability and specific routes to HLA class I loss and immunoescape URL: diff --git a/man/GSE28702_eset.Rd b/man/GSE28702_eset.Rd index 3c2703c..b09acd2 100644 --- a/man/GSE28702_eset.Rd +++ b/man/GSE28702_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Tsuji S, Midorikawa Y, Takahashi T, Yagi K et al.??Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis.??Br J Cancer??2012 Jan 3 + Experimenter name: Tsuji S, Midorikawa Y, Takahashi T, Yagi K et al. Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis. Br J Cancer 2012 Jan 3 Laboratory: Tsuji 2011 Contact information: Title: Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis. diff --git a/man/GSE3294_eset.Rd b/man/GSE3294_eset.Rd index 3993feb..69042a9 100644 --- a/man/GSE3294_eset.Rd +++ b/man/GSE3294_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Bianchini M, Levy E, Zucchini C, Pinski V et al.??Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa.??Int J Oncol??2006 Jul + Experimenter name: Bianchini M, Levy E, Zucchini C, Pinski V et al. Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa. Int J Oncol 2006 Jul Laboratory: Bianchini 2005 Contact information: Title: Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa. diff --git a/man/GSE33113_eset.Rd b/man/GSE33113_eset.Rd index 0910f85..63d17e3 100644 --- a/man/GSE33113_eset.Rd +++ b/man/GSE33113_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: de Sousa E Melo F, Colak S, Buikhuisen J, Koster J et al.??Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.??Cell Stem Cell??2011 Nov 4 - Laboratory: Medema JP,??Tanis PJ 2011 + Experimenter name: de Sousa E Melo F, Colak S, Buikhuisen J, Koster J et al. Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients. Cell Stem Cell 2011 Nov 4 + Laboratory: Medema JP, Tanis PJ 2011 Contact information: Title: Mutations in the Ras-Raf Axis underlie the prognostic value of CD133 in colorectal cancer. URL: diff --git a/man/GSE39582_eset.Rd b/man/GSE39582_eset.Rd index 739a2f2..8675939 100644 --- a/man/GSE39582_eset.Rd +++ b/man/GSE39582_eset.Rd @@ -2,13 +2,13 @@ \alias{ GSE39582_eset } \docType{data} \title{ Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. } -\description{ Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95\% CI 1.1-2.1, p???=???0.0097). However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways. } +\description{ Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95\% CI 1.1-2.1, p = 0.0097). However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways. } \usage{data( GSE39582_eset )} \format{ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Marisa L, de Reyni??A, Duval A, Selves J et al.??Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.??PLoS Med??2013 + Experimenter name: Marisa L, de Reynies A, Duval A, Selves J et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013 Laboratory: Marisa, Boige 2012 Contact information: Title: Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. diff --git a/man/GSE3964_eset.Rd b/man/GSE3964_eset.Rd index 56a7969..1eff618 100644 --- a/man/GSE3964_eset.Rd +++ b/man/GSE3964_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Graudens E, Boulanger V, Mollard C, Mariage-Samson R et al.??Deciphering cellular states of innate tumor drug responses.??Genome Biol??2006 + Experimenter name: Graudens E, Boulanger V, Mollard C, Mariage-Samson R et al. Deciphering cellular states of innate tumor drug responses. Genome Biol 2006 Laboratory: Graudens, Imbeaud 2006 Contact information: Title: Deciphering cellular states of innate tumor drug responses. diff --git a/man/GSE4045_eset.Rd b/man/GSE4045_eset.Rd index b79ef75..dbdd8bc 100644 --- a/man/GSE4045_eset.Rd +++ b/man/GSE4045_eset.Rd @@ -8,7 +8,7 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Laiho P, Kokko A, Vanharanta S, Salovaara R et al.??Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.??Oncogene2007 Jan 11 + Experimenter name: Laiho P, Kokko A, Vanharanta S, Salovaara R et al. Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis. Oncogene 2007 Jan 11 Laboratory: Laiho, Aaltonen 2007 Contact information: Title: Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis. diff --git a/man/GSE4526_eset.Rd b/man/GSE4526_eset.Rd index 2fa649f..1a8884b 100644 --- a/man/GSE4526_eset.Rd +++ b/man/GSE4526_eset.Rd @@ -8,8 +8,8 @@ \preformatted{ experimentData(eset): Experiment data - Experimenter name: Watanabe T, Kobunai T, Sakamoto E, Yamamoto Y et al.??Gene expression signature for recurrence in stage III colorectal cancers.??Cancer??2009 Jan 15 - Laboratory: Watanabe T,??Kobunai T,??Toda E,??Oka T 2006 + Experimenter name: Watanabe T, Kobunai T, Sakamoto E, Yamamoto Y et al. Gene expression signature for recurrence in stage III colorectal cancers. Cancer 2009 Jan 15 + Laboratory: Watanabe T, Kobunai T, Toda E, Oka T 2006 Contact information: Title: Gene expression signature for recurrence in stage III colorectal cancers. URL: diff --git a/man/GSE45270_eset.Rd b/man/GSE45270_eset.Rd index e1910de..7700713 100644 --- a/man/GSE45270_eset.Rd +++ b/man/GSE45270_eset.Rd @@ -9,7 +9,7 @@ experimentData(eset): Experiment data Experimenter name: Profiling project of a panel of tubular adenoma and serrated adenoma patient material collected in the Academic Medical Center - Laboratory: Medema JP,??de Sousa E Melo F,??Vermeulen L,??Jansen M,??Dekker E,??Van Noesel C,??Fessler E 2013 + Laboratory: Medema JP, de Sousa E Melo F, Vermeulen L, Jansen M, Dekker E, Van Noesel C, Fessler E 2013 Contact information: Title: AMC tubular and serrated adenomas URL: diff --git a/man/TCGA.COAD_eset.Rd b/man/TCGA.COAD_eset.Rd index c072043..4af64cc 100644 --- a/man/TCGA.COAD_eset.Rd +++ b/man/TCGA.COAD_eset.Rd @@ -2,7 +2,7 @@ \alias{ TCGA.COAD_eset } \docType{data} \title{ Comprehensive molecular characterization of human colon and rectal cancer. } -\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ?? (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } +\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase epsilon (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } \usage{data( TCGA.COAD_eset )} \format{ \preformatted{ diff --git a/man/TCGA.READ_eset.Rd b/man/TCGA.READ_eset.Rd index 92cee99..6c64683 100644 --- a/man/TCGA.READ_eset.Rd +++ b/man/TCGA.READ_eset.Rd @@ -2,7 +2,7 @@ \alias{ TCGA.READ_eset } \docType{data} \title{ Comprehensive molecular characterization of human colon and rectal cancer. } -\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ?? (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } +\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase epsilon (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } \usage{data( TCGA.READ_eset )} \format{ \preformatted{ diff --git a/man/TCGA.RNASeqV2.READ_eset.Rd b/man/TCGA.RNASeqV2.READ_eset.Rd index 933e184..d5fcdb2 100644 --- a/man/TCGA.RNASeqV2.READ_eset.Rd +++ b/man/TCGA.RNASeqV2.READ_eset.Rd @@ -2,7 +2,7 @@ \alias{ TCGA.RNASeqV2.READ_eset } \docType{data} \title{ Comprehensive molecular characterization of human colon and rectal cancer. } -\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ?? (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } +\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase epsilon (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } \usage{data( TCGA.RNASeqV2.READ_eset )} \format{ \preformatted{ diff --git a/man/TCGA.RNASeqV2_eset.Rd b/man/TCGA.RNASeqV2_eset.Rd index 9467409..dbf02ab 100644 --- a/man/TCGA.RNASeqV2_eset.Rd +++ b/man/TCGA.RNASeqV2_eset.Rd @@ -2,7 +2,7 @@ \alias{ TCGA.RNASeqV2_eset } \docType{data} \title{ Comprehensive molecular characterization of human colon and rectal cancer. } -\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase ?? (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } +\description{ To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16\% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase epsilon (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. } \usage{data( TCGA.RNASeqV2_eset )} \format{ \preformatted{