Authors: |
Muzny, D. M.; Bainbridge, M. N.; Chang, K.; Dinh, H. H.; Drummond, J. A.; Fowler, G.; Kovar, C. L.; Lewis, L. R.; Morgan, M. B.; Newsham, I. F.; Reid, J. G.; Santibanez, J.; Shinbrot, E.; Trevino, L. R.; Wu, Y. Q.; Wang, M.; Gunaratne, P.; Donehower, L. A.; Creighton, C. J.; Wheeler, D. A.; Gibbs, R. A.; Lawrence, M. S.; Voet, D.; Jing, R.; Cibulskis, K.; Sivachenko, A.; Stojanov, P.; McKenna, A.; Lander, E. S.; Gabriel, S.; Ding, L.; Fulton, R. S.; Koboldt, D. C.; Wylie, T.; Walker, J.; Dooling, D. J.; Fulton, L.; Delehaunty, K. D.; Fronick, C. C.; Demeter, R.; Mardis, E. R.; Wilson, R. K.; Chu, A.; Chun, H. J. E.; Mungall, A. J.; Pleasance, E.; Gordon Robertson, A.; Stoll, D.; Balasundaram, M.; Birol, I.; Butterfield, Y. S. N.; Chuah, E.; Coope, R. J. N.; Dhalla, N.; Guin, R.; Hirst, C.; Hirst, M.; Holt, R. A.; Lee, D.; Li, H. I.; Mayo, M.; Moore, R. A.; Schein, J. E.; Slobodan, J. R.; Tam, A.; Thiessen, N.; Varhol, R.; Zeng, T.; Zhao, Y.; Jones, S. J. M.; Marra, M. A.; Bass, A. J.; Ramos, A. H.; Saksena, G.; Cherniack, A. D.; Schumacher, S. E.; Tabak, B.; Carter, S. L.; Pho, N. H.; Nguyen, H.; Onofrio, R. C.; Crenshaw, A.; Ardlie, K.; Beroukhim, R.; Winckler, W.; Meyerson, M.; Protopopov, A.; Hadjipanayis, A.; Lee, E.; Xi, R.; Yang, L.; Ren, X.; Sathiamoorthy, N.; Chen, P. C.; Haseley, P.; Xiao, Y.; Lee, S.; Seidman, J.; Chin, L.; Park, P. J.; De Ronde, J.; Schultz, N.; Cerami, E.; Ciriello, G.; Goldberg, A. P.; Gross, B.; Jacobsen, A.; Gao, J.; Kaczkowski, B.; Sinha, R.; Aksoy, B. A.; Antipin, Y.; Reva, B.; Shen, R.; Taylor, B. S.; Chan, T. A.; Ladanyi, M.; Sander, C.; Kaufman, A.; Temple, L.; Guillem, J. G.; Nash, G. M.; Paty, P. B.; Weiser, M. R.; Zeng, Z.; Mariano, M. C.; Medina, E. N.; Vakiani, E.; Solit, D. |
Article Title: |
Comprehensive molecular characterization of human colon and rectal cancer |
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 μ (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. © 2012 Macmillan Publishers Limited. All rights reserved. |
Keywords: |
human tissue; gene mutation; gene sequence; methylation; mutation; polymorphism, single nucleotide; genetic analysis; chromosome; gene; gene expression; gene expression profiling; colonic neoplasms; dna methylation; colorectal carcinoma; genome analysis; messenger rna; molecular analysis; genome; mutation rate; oncogene k ras; gene dosage; rectal neoplasms; pik3ca gene; genetic marker; mlh1 gene; sequence analysis, dna; dna copy number variations; translocation; apc gene; tp53 gene; exome; erbb2 gene; arid1a gene; fam123b gene; polymerase epsilon gene; smad4 gene; sox9 gene
|
Journal Title: |
Nature
|
Volume: |
487 |
Issue: |
7407 |
ISSN: |
0028-0836 |
Publisher: |
Nature Publishing Group
|
Date Published: |
2012-07-18 |
Start Page: |
330 |
End Page: |
337 |
Language: |
English |
DOI: |
10.1038/nature11252
|
PROVIDER: |
scopus
|
PMCID: |
PMC3401966
|
PUBMED: |
22810696
|
DOI/URL: |
|
Notes: |
---
- "Export Date: 1 August 2012"
- "CODEN: NATUA"
- "Source: Scopus"
|