Comprehensive molecular characterization of human colon and rectal cancer Journal Article


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"
Altmetric Score
MSK Authors
  1. Timothy Chan
    233 Chan
  2. Philip B Paty
    380 Paty
  3. David Solit
    459 Solit
  4. Ronglai Shen
    131 Shen
  5. Jose Guillem
    379 Guillem
  6. Zhaoshi Zeng
    85 Zeng
  7. Marc Ladanyi
    907 Ladanyi
  8. Martin R Weiser
    351 Weiser
  9. Boris A Reva
    36 Reva
  10. Garrett Nash
    141 Nash
  11. Larissa Temple
    185 Temple
  12. Chris Sander
    196 Sander
  13. Efsevia Vakiani
    171 Vakiani
  14. Rileen Sinha
    19 Sinha
  15. Jianjiong Gao
    66 Gao
  16. Barry Stephen Taylor
    152 Taylor
  17. Ethan Cerami
    21 Cerami
  18. Nikolaus D Schultz
    215 Schultz
  19. Benjamin E Gross
    28 Gross
  20. Yevgeniy Antipin
    19 Antipin
  21. Bulent Arman Aksoy
    33 Aksoy
  22. Elizabeth Medina
    1 Medina