Genomic alterations in fatal forms of non-anaplastic thyroid cancer: Identification of MED12 and RBM10 as novel thyroid cancer genes associated with tumor virulence Journal Article
| Authors: | Ibrahimpasic, T.; Xu, B.; Landa, I.; Dogan, S.; Middha, S.; Seshan, V.; Deraje, S.; Carlson, D. L.; Migliacci, J.; Knauf, J. A.; Untch, B.; Berger, M. F.; Morris, L.; Tuttle, R. M.; Chan, T.; Fagin, J. A.; Ghossein, R.; Ganly, I. |
| Article Title: | Genomic alterations in fatal forms of non-anaplastic thyroid cancer: Identification of MED12 and RBM10 as novel thyroid cancer genes associated with tumor virulence |
| Abstract: | Purpose: Patients with anaplastic thyroid cancer (ATC) have a were identified. There was a high frequency of mutations in very high death rate. In contrast, deaths from non-anaplastic MED12 and these were mutually exclusive to TERT promoter thyroid (NAT) cancer are much less common. The genetic altera-mutations and also to BRAF and RAS mutations. In addition, a tions in fatal NAT cancers have not been reported. high frequency of mutations in RBM10 was identified and these Experimental Design: We performed next-generation sequenc-co-occurred with RAS mutations and PIK3CA mutations. Coming of 410 cancer genes from 57 fatal NAT primary cancers. Results pared with the PTCs in TCGA, there were higher frequencies of were compared with The Cancer Genome Atlas study (TCGA mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, study) of papillary thyroid cancers (PTCs) and to the genomic SWI/SNF subunits, and histone methyltransferases. changes reported in ATC. Conclusions: These data support a model, whereby fatal NAT Results: There was a very high prevalence of TERT promoter cancers arise from well-differentiated tumors through the accu-mutations, comparable with that of ATC, and these co-occurred mulation of key additional genetic abnormalities. The high rate of with BRAF and RAS mutations. A high incidence of chromosome TERT promoter mutations, MED12 mutations, RBM10 muta-1q gain was seen highlighting its importance in tumor aggres-tions, and chromosome 1q gain highlight their likely association siveness. Two novel fusion genes DLG5–RET and OSBPL1A–BRAF with tumor virulence. © 2017 American Association for Cancer Research. |
| Keywords: | protein kinase b; adult; controlled study; middle aged; gene mutation; major clinical study; promoter region; somatic mutation; gene; genetic association; mutational analysis; phosphatidylinositol 3 kinase; protein p53; genome analysis; epigenetics; gene identification; mammalian target of rapamycin; carcinogenicity; gene fusion; telomerase reverse transcriptase; thyroidectomy; ras protein; thyroid cancer; thyroid papillary carcinoma; b raf kinase; oncogene ras; chromosome 1q; braf gene; copy number variation; tp53 gene; next generation sequencing; akt gene; mtor gene; tert gene; human; male; female; priority journal; article; rbm10 gene; pole gene; dlg5 gene; med12 gene; non anaplastic thyroid cancer; osbpl1a gene; pi3k gene |
| Journal Title: | Clinical Cancer Research |
| Volume: | 23 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2017-10-01 |
| Start Page: | 5970 |
| End Page: | 5980 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-17-1183 |
| PROVIDER: | scopus |
| PMCID: | PMC5626586 |
| PUBMED: | 28634282 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 December 2017 -- Source: Scopus |
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