Comprehensive molecular characterization of human colon and rectal cancer

Comprehensive molecular characterization of human colon and rectal cancer

19 JULY 2012 | The Cancer Genome Atlas Network*
The Cancer Genome Atlas Network conducted a comprehensive genome-scale analysis of 276 colorectal cancer (CRC) samples to characterize somatic alterations. The study included exome sequencing, DNA copy number analysis, promoter methylation, and messenger RNA and microRNA expression analysis. A subset of samples underwent low-depth whole-genome sequencing. Sixteen percent of CRCs were hypermutated, with three-quarters having high microsatellite instability and one-quarter having somatic mutations in mismatch-repair genes or *POLE*. Excluding hypermutated cancers, colon and rectum cancers showed similar genomic alterations, with 24 significantly mutated genes, including *APC*, *TP53*, *SMAD4*, *PIK3CA*, and *KRAS*. Recurrent copy-number alterations included amplifications of *ERBB2* and *IGF2*, and chromosomal translocations involving *NAV2* and *TCF7L1*. Integrative analyses identified new markers for aggressive CRC and highlighted the role of MYC-directed transcriptional activation and repression. The study provides a detailed understanding of CRC biology and identifies potential therapeutic targets.The Cancer Genome Atlas Network conducted a comprehensive genome-scale analysis of 276 colorectal cancer (CRC) samples to characterize somatic alterations. The study included exome sequencing, DNA copy number analysis, promoter methylation, and messenger RNA and microRNA expression analysis. A subset of samples underwent low-depth whole-genome sequencing. Sixteen percent of CRCs were hypermutated, with three-quarters having high microsatellite instability and one-quarter having somatic mutations in mismatch-repair genes or *POLE*. Excluding hypermutated cancers, colon and rectum cancers showed similar genomic alterations, with 24 significantly mutated genes, including *APC*, *TP53*, *SMAD4*, *PIK3CA*, and *KRAS*. Recurrent copy-number alterations included amplifications of *ERBB2* and *IGF2*, and chromosomal translocations involving *NAV2* and *TCF7L1*. Integrative analyses identified new markers for aggressive CRC and highlighted the role of MYC-directed transcriptional activation and repression. The study provides a detailed understanding of CRC biology and identifies potential therapeutic targets.
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[slides and audio] Comprehensive molecular characterization of human colon and rectal cancer