Comprehensive molecular characterization of human colon and rectal cancer
Name
Lander_Comprehensive molecular.pdf
Size
1.31 MB
Format
Adobe PDF
Checksum (MD5)
2f0d186212c1fa365b8e8834280f98a8
Author(s)
Lander, Eric Steven
Date Issued
July 2012
Journal
Nature
Publisher
Nature Publishing Group
Citation
Muzny, Donna M., Matthew N. Bainbridge, Kyle Chang, Huyen H. Dinh, Jennifer A. Drummond, Gerald Fowler, Christie L. Kovar, et al. “Comprehensive molecular characterization of human colon and rectal cancer.” Nature 487, no. 7407 (July 18, 2012): 330-337.
Version
Final published version
Abstract
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 ε (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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/nature11252
