A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

British Journal of Cancer
Milan RadovichPatrick J Loehrer

Abstract

Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumour. This work has led to the initiation of a phase II clinical trial of PI3K inhib...Continue Reading

Associated Clinical Trials

Aug 20, 2014·Patrick Joseph Loehrer Sr., Patrick Joseph Loehrer Sr.

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Citations

Mar 22, 2019·PloS One·Jean-Michel MauryCaroline Leroux
Aug 23, 2019·Wiley Interdisciplinary Reviews. RNA·Shama Prasada KabekkoduKapaettu Satyamoorthy
May 11, 2017·Molecular Cancer·Teresa BellissimoFrancesco Fazi
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Mar 7, 2021·Virchows Archiv : an International Journal of Pathology·Alexander MarxYosuke Yamada
Feb 21, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Yosuke YamadaAlexander Marx
May 26, 2021·Epigenomics·Tania L GonzalezMargareta D Pisarska
Jul 18, 2021·Seminars in Diagnostic Pathology·Julia Prays, Cristian Ortiz-Villalón
Oct 26, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Alexander MarxPhilipp Ströbel

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Methods Mentioned

BETA
RNA-seq
PCR
enzyme-linked immunosorbent assays
transfection
ELISA

Clinical Trials Mentioned

NCT02220855

Software Mentioned

GraphPad
DataAssist
Partek Genomics Suite
Prism
SDS2
Partek Pathway Analysis
Partek

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