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Nat Genet. 2014 Aug;46(8):844-9. doi: 10.1038/ng.3016. Epub 2014 Jun 29.

A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors.

Author information

1
Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
2
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
3
Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
4
Thoracic Surgery, Pisa University Hospital, Pisa, Italy.
5
Surgical Pathology, Pisa University Hospital, Pisa, Italy.
6
Medical Oncology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
7
Surgical Pathology, Padua University Hospital, Padua, Italy.
8
Medical Oncology, Padua University Hospital, Padua, Italy.
9
Thoracic Surgery, Padua University Hospital, Padua, Italy.
10
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
11
1] Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. [2] Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.

Abstract

We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970T>A) in GTF2I at high frequency in type A thymomas, a relatively indolent subtype. In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified. Therefore, GTF2I mutation correlated with better survival. GTF2I β and δ isoforms were expressed in TETs, and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas carried a higher number of mutations than thymomas (average of 43.5 and 18.4, respectively). Notably, we identified recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1, in thymic carcinomas. These findings will complement the diagnostic assessment of these tumors and also facilitate development of a molecular classification and assessment of prognosis and treatment strategies.

Comment in

PMID:
24974848
PMCID:
PMC5705185
DOI:
10.1038/ng.3016
[Indexed for MEDLINE]
Free PMC Article

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