Integrated genomic characterization of endometrial carcinoma Journal Article


Authors: Getz, G.; Gabriel, S. B.; Cibulskis, K.; Lander, E.; Sivachenko, A.; Sougnez, C.; Lawrence, M.; Kandoth, C.; Dooling, D.; Fulton, R.; Fulton, L.; Kalicki-Veizer, J.; McLellan, M. D.; O'Laughlin, M.; Schmidt, H.; Wilson, R. K.; Ye, K.; Li, D.; Ally, A.; Balasundaram, M.; Birol, I.; Butterfield, Y. S. N.; Carlsen, R.; Carter, C.; Chu, A.; Chuah, E.; Chun, H. J. E.; Dhalla, N.; Guin, R.; Hirst, C.; Holt, R. A.; Jones, S. J. M.; Lee, D.; Li, H. I.; Marra, M. A.; Mayo, M.; Moore, R. A.; Mungall, A. J.; Plettner, P.; Schein, J. E.; Sipahimalani, P.; Tam, A.; Varhol, R. J.; Robertson, A. G.; Cherniack, A. D.; Pashtan, I.; Saksena, G.; Onofrio, R. C.; Schumacher, S. E.; Tabak, B.; Carter, S. L.; Hernandez, B.; Gentry, J.; Salvesen, H. B.; Ardlie, K.; Winckler, W.; Beroukhim, R.; Meyerson, M.; Hadjipanayis, A.; Lee, S.; Mahadeshwar, H. S.; Park, P.; Protopopov, A.; Ren, X.; Seth, S.; Song, X.; Tang, J.; Xi, R.; Yang, L.; Dong, Z.; Kucherlapati, R.; Chin, L.; Zhang, J.; Auman, J. T.; Balu, S.; Bodenheimer, T.; Buda, E.; Hayes, D. N.; Hoyle, A. P.; Jefferys, S. R.; Jones, C. D.; Meng, S.; Mieczkowski, P. A.; Mose, L. E.; Parker, J. S.; Perou, C. M.; Roach, J.; Yan, S.; Simons, J. V.; Soloway, M. G.; Tan, D.; Topal, M. D.; Waring, S.; Wu, J.; Hoadley, K. A.; Baylin, S. B.; Bootwalla, M. S.; Lai, P. H.; Triche, T. J. Jr; Van Den Berg, D. J.; Askoy, B. A.; Antipin, Y.; Ciriello, G.; Dresdner, G.; Gao, J.; Gross, B.; Jacobsen, A.; Reva, B.; Sander, C.; Sinha, R.; Sumer, S. O.; Cerami, E.; Weinhold, N.; Schultz, N.; Ladanyi, M.; Shen, R.; Dao, F.; Olvera, N.; Bogomolniy, F.; Levine, D.; Garg, K.; Soslow, R.
Article Title: Integrated genomic characterization of endometrial carcinoma
Abstract: We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. © 2013 Macmillan Publishers Limited. All rights reserved.
Journal Title: Nature
Volume: 497
Issue: 7447
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2013-05-02
Start Page: 67
End Page: 73
Language: English
DOI: 10.1038/nature12113
PROVIDER: scopus
PUBMED: 23636398
PMCID: PMC3704730
DOI/URL:
Notes: --- - "Export Date: 3 June 2013" - "CODEN: NATUA" - "Source: Scopus"
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MSK Authors
  1. Douglas A Levine
    365 Levine
  2. Ronglai Shen
    147 Shen
  3. Marc Ladanyi
    1063 Ladanyi
  4. Robert Soslow
    718 Soslow
  5. Boris A Reva
    36 Reva
  6. Narciso Olvera
    72 Olvera
  7. Chris Sander
    204 Sander
  8. Karuna Garg
    76 Garg
  9. Rileen Sinha
    19 Sinha
  10. Jianjiong Gao
    83 Gao
  11. Fanny Dao
    58 Dao
  12. Ethan Cerami
    21 Cerami
  13. Nikolaus D Schultz
    283 Schultz
  14. Benjamin E Gross
    31 Gross
  15. Yevgeniy Antipin
    19 Antipin
  16. Bulent Arman Aksoy
    35 Aksoy
  17. Selcuk Onur Sumer
    23 Sumer