title: A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors.
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.
authors: Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors: Iacopo
authors: I
authors: Petrini
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Paul S
authors: PS
authors: Meltzer
authors: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors: In-Kyu
authors: IK
authors: Kim
authors: Thoracic Surgery, Pisa University Hospital, Pisa, Italy.
authors: Marco
authors: M
authors: Lucchi
authors: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors: Kang-Seo
authors: KS
authors: Park
authors: Surgical Pathology, Pisa University Hospital, Pisa, Italy.
authors: Gabriella
authors: G
authors: Fontanini
authors: Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors: James
authors: J
authors: Gao
authors: Medical Oncology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: Paolo A
authors: PA
authors: Zucali
authors: Surgical Pathology, Padua University Hospital, Padua, Italy.
authors: Fiorella
authors: F
authors: Calabrese
authors: Medical Oncology, Padua University Hospital, Padua, Italy.
authors: Adolfo
authors: 0000000181757467
authors: A
authors: Favaretto
authors: Thoracic Surgery, Padua University Hospital, Padua, Italy.
authors: Federico
authors: F
authors: Rea
authors: Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
authors: Jaime
authors: J
authors: Rodriguez-Canales
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Robert L
authors: RL
authors: Walker
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Marbin
authors: M
authors: Pineda
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Yuelin J
authors: YJ
authors: Zhu
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Christopher
authors: C
authors: Lau
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Keith J
authors: KJ
authors: Killian
authors: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Sven
authors: S
authors: Bilke
authors: Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors: Donna
authors: D
authors: Voeller
authors: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors: Sivanesan
authors: S
authors: Dakshanamurthy
authors: 1] Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. [2] Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors: Yisong
authors: Y
authors: Wang
authors: 1] Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. [2] Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors: Giuseppe
authors: G
authors: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D011379:Prognosis; D013953:Thymus Neoplasms / Q000235:genetics*; D019473:Transcription Factors, TFII / Q000235:genetics*; D055815:Young Adult
chemical_list: C104259:GTF2I protein, human; D019473:Transcription Factors, TFII