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

Iacopo Petrini, Paul S. Meltzer, In Kyu Kim, Marco Lucchi, Kang Seo Park, Gabriella Fontanini, James Gao, Paolo A. Zucali, Fiorella Calabrese, Adolfo Favaretto, Federico Rea, Jaime Rodriguez-Canales, Robert L. Walker, Marbin Pineda, Yuelin J. Zhu, Christopher Lau, Keith J. Killian, Sven Bilke, Donna Voeller, Sivanesan Dakshanamurthy & 2 others Yisong Wang, Giuseppe Giaccone

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)844-849
Number of pages6
JournalNature Genetics
Volume46
Issue number8
DOIs
Publication statusPublished - 2014

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Thymoma
Missense Mutation
Mutation
Neoplasm Genes
Protein Isoforms
Chromosomes, Human, Pair 7
Cell Proliferation
Thymic epithelial tumor
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

Cite this

Petrini, I., Meltzer, P. S., Kim, I. K., Lucchi, M., Park, K. S., Fontanini, G., ... Giaccone, G. (2014). A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nature Genetics, 46(8), 844-849. https://doi.org/10.1038/ng.3016

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 journalArticle

Petrini, I, Meltzer, PS, Kim, IK, Lucchi, M, Park, KS, Fontanini, G, Gao, J, Zucali, PA, Calabrese, F, Favaretto, A, Rea, F, Rodriguez-Canales, J, Walker, RL, Pineda, M, Zhu, YJ, Lau, C, Killian, KJ, Bilke, S, Voeller, D, Dakshanamurthy, S, Wang, Y & Giaccone, G 2014, 'A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors', Nature Genetics, vol. 46, no. 8, pp. 844-849. https://doi.org/10.1038/ng.3016
Petrini I, Meltzer PS, Kim IK, Lucchi M, Park KS, Fontanini G et al. A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nature Genetics. 2014;46(8):844-849. https://doi.org/10.1038/ng.3016
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. / A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. In: Nature Genetics. 2014 ; Vol. 46, No. 8. pp. 844-849.
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