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 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 August 2017 -- Source: Scopus |
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