GRCh37 · COSMIC v99

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Genomic alterations in fatal forms of non-anaplastic thyroid cancer: Identification of MED12 and RBM10 as novel thyroid cancer genes associated with tumor virulence.
Paper ID
COSP43799
Authors
Ibrahimpasic T, Xu B, Landa I, Dogan S, Middha S, Seshan V, Deraje Vasudeva S, Carlson D, Migliacci J, Knauf JA, Untch BR, Berger MF, Morris LG, Tuttle RM, Chan TA, Fagin JA, Ghossein R and Ganly I
Affiliation
Department of Surgery, Memorial Sloan Kettering Cancer Center.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research, 2017
ISSN: 1078-0432
PMID: 28634282 (view at PubMed or Europe PMC)
Abstract
Purpose. Patients with anaplastic thyroid cancer have a very high death rate. In contrast, deaths from non-anaplastic thyroid cancer are much less common. The genetic alterations in fatal non-anaplastic thyroid cancers have not been reported. <p>Experimental Design. We performed next-generation sequencing of 410 cancer genes from 57 fatal non-anaplastic thyroid primary cancers. Results were compared to The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC) and to the genomic changes reported in anaplastic thyroid cancer (ATC).</p> <p>Results. There was a very high prevalence of TERT promoter mutations, comparable to that of anaplastic thyroid cancer, and these co-occurred with BRAF and RAS mutations. A high incidence of chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 were identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared to the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.</p> <p>Conclusions. These data support a model whereby fatal non-anaplastic thyroid cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations and chromosome 1q gain highlight their likely association with tumor virulence.
Paper Status
Curated