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Open Access 01-07-2017 | Original Article

Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets

Authors: Franz Enkner, Bettina Pichlhöfer, Alexandru Teodor Zaharie, Milica Krunic, Tina Maria Holper, Stefan Janik, Bernhard Moser, Karin Schlangen, Barbara Neudert, Karin Walter, Brigitte Migschitz, Leonhard Müllauer

Published in: Pathology & Oncology Research | Issue 3/2017

Abstract

Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation. Fluorescence in situ hybridization detected in 38 % of carcinomas a CDKN2A, in 32 % a TP53 and in 8 % an ATM gene deletion, whereas only one B3 thymoma exhibited a CDKNA deletion, and none of the type A thymomas showed a gene loss. Sequencing of the total miRNA pool of 5 type A thymomas and 5 thymic carcinomas identified the C19MC miRNA cluster as highly expressed in type A thymomas, but completely silenced in thymic carcinomas. Furthermore, the miRNA cluster C14MC was downregulated in thymic carcinomas. Among non-clustered miRNAs, the upregulation of miR-21, miR-9-3 and miR-375 and the downregulation of miR-34b, miR-34c, miR-130a and miR-195 in thymic carcinomas were most significant. The expression of ALK, HER2, HER3, MET, phospho-mTOR, p16^INK4A, PDGFRA, PDGFRB, PD-L1, PTEN and ROS1 was investigated by immunohistochemistry. PDGFRA was increased in thymic carcinomas and PD-L1 in B3 thymomas and thymic carcinomas. In summary, our results reveal genetic differences between thymomas and thymic carcinomas and suggest potential novel targets for therapy.

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Title: Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets
Authors: Franz Enkner
Bettina Pichlhöfer
Alexandru Teodor Zaharie
Milica Krunic
Tina Maria Holper
Stefan Janik
Bernhard Moser
Karin Schlangen
Barbara Neudert
Karin Walter
Brigitte Migschitz
Leonhard Müllauer
Publication date: 01-07-2017
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 3/2017
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-016-0144-8

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