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 2 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.
| Original language | English |
|---|---|
| Pages (from-to) | 844-849 |
| Number of pages | 6 |
| Journal | Nature Genetics |
| Volume | 46 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Genetics
- Medicine(all)
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A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. / Petrini, Iacopo; Meltzer, Paul S.; Kim, In Kyu; Lucchi, Marco; Park, Kang Seo; Fontanini, Gabriella; Gao, James; Zucali, Paolo A.; Calabrese, Fiorella; Favaretto, Adolfo; Rea, Federico; Rodriguez-Canales, Jaime; Walker, Robert L.; Pineda, Marbin; Zhu, Yuelin J.; Lau, Christopher; Killian, Keith J.; Bilke, Sven; Voeller, Donna; Dakshanamurthy, Sivanesan; Wang, Yisong; Giaccone, Giuseppe.
In: Nature Genetics, Vol. 46, No. 8, 2014, p. 844-849.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors
AU - Petrini, Iacopo
AU - Meltzer, Paul S.
AU - Kim, In Kyu
AU - Lucchi, Marco
AU - Park, Kang Seo
AU - Fontanini, Gabriella
AU - Gao, James
AU - Zucali, Paolo A.
AU - Calabrese, Fiorella
AU - Favaretto, Adolfo
AU - Rea, Federico
AU - Rodriguez-Canales, Jaime
AU - Walker, Robert L.
AU - Pineda, Marbin
AU - Zhu, Yuelin J.
AU - Lau, Christopher
AU - Killian, Keith J.
AU - Bilke, Sven
AU - Voeller, Donna
AU - Dakshanamurthy, Sivanesan
AU - Wang, Yisong
AU - Giaccone, Giuseppe
PY - 2014
Y1 - 2014
N2 - 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 2 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.
AB - 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 2 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.
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U2 - 10.1038/ng.3016
DO - 10.1038/ng.3016
M3 - Article
VL - 46
SP - 844
EP - 849
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 8
ER -