Integrated genomic characterization of papillary thyroid carcinoma Journal Article

Author: The Cancer Genome Atlas Research Network
Contributors: Aksoy, B. A.; Bryant, R.; Chan, T. A.; Ciriello, G.; Dresdner, G.; Eng, S.; Fagin, J. A.; Ganly, I.; Gao, J.; Ghossein, R.; Gross, B.; Jacobsen, A.; Ladanyi, M.; Lee, W.; Ramirez, R.; Rosenthal, M.; Sander, C.; Schultz, N.; Senbabaoglu, Y.; Shen, R.; Sinha, R.; Sumer, S. O.; Sun, Y.; Tuttle, R. M.; Weinhold, N.
Article Title: Integrated genomic characterization of papillary thyroid carcinoma
Abstract: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease. © 2014 The Authors.
Keywords: signal transduction; human tissue; major clinical study; promoter region; somatic mutation; genetics; mutation; cytology; metabolism; gene expression; tumor differentiation; genetic variability; gene frequency; pathology; dna methylation; oncogene h ras; cancer genetics; oncogene; gene fusion; carcinoma; telomerase reverse transcriptase; genomics; checkpoint kinase 2; thyroid carcinoma; thyroid neoplasms; cancer classification; thyroid gland; k ras protein; b raf kinase; thyroid tumor; dna copy number variations; copy number variation; indel mutation; humans; human; article; initiation factor 1a
Journal Title: Cell
Volume: 159
Issue: 3
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2014-10-23
Start Page: 676
End Page: 690
Language: English
DOI: 10.1016/j.cell.2014.09.050
PUBMED: 25417114
PROVIDER: scopus
PMCID: PMC4243044
Notes: Article -- Export Date: 14 August 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. James A Fagin
    109 Fagin
  2. Timothy Chan
    222 Chan
  3. Ronald A Ghossein
    302 Ghossein
  4. Robert M Tuttle
    362 Tuttle
  5. Ronglai Shen
    129 Shen
  6. Marc Ladanyi
    879 Ladanyi
  7. Ian Ganly
    234 Ganly
  8. Chris Sander
    196 Sander
  9. Rileen Sinha
    19 Sinha
  10. Jianjiong Gao
    63 Gao
  11. Nikolaus D Schultz
    206 Schultz
  12. Benjamin E Gross
    26 Gross
  13. William Lee
    38 Lee
  14. Bulent Arman Aksoy
    33 Aksoy
  15. Selcuk Onur Sumer
    21 Sumer
  16. Yichao Sun
    12 Sun
  17. Ricardo   Ramirez
    19 Ramirez
  18. Robert Leslie Bryant
    3 Bryant
  19. Stephanie Lauren Eng
    2 Eng