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Novel MIR143‐NOTCH fusions in benign and malignant glomus tumors
Author(s) -
Mosquera JuanMiguel,
Sboner Andrea,
Zhang Lei,
Chen ChunLiang,
Sung YunShao,
Chen HsiaoWei,
Agaram Narasimhan P.,
Briskin Daniel,
Basha Basma M.,
Singer Samuel,
Rubin Mark A.,
Tuschl Thomas,
Antonescu Cristina R.
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22102
Subject(s) - pathogenesis , pathology , angioleiomyoma , gene rearrangement , biology , fish <actinopterygii> , immunohistochemistry , glomus tumor , gene , medicine , genetics , leiomyoma , fishery
Glomus tumors (GT) have been classified among tumors of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies have been carried out to date to investigate their genetic phenotype and to confirm their shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT and M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired‐end RNA‐seq data. A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1. After being validated by FISH and RT‐PCR, these abnormalities were screened on 33 GTs, 6 myopericytomas, 9 myofibroma/toses, 18 angioleiomyomas and in a control group of 5 sino‐nasal hemangiopericytomas. Overall NOTCH2 gene rearrangements were identified in 52% of GT, including all malignant cases and one NF1‐related GT. No additional cases showed NOTCH1 rearrangement. As NOTCH3 shares similar functions with NOTCH2 in regulating vascular smooth muscle development, the study group was also investigated for abnormalities in this gene by FISH. Indeed, NOTCH3 rearrangements were identified in 9% of GTs, all present in benign soft tissue GT, one case being fused to MIR143 . Only 1/18 angioleiomyomas showed NOTCH2 gene rearrangement, while all the myopericytomas and myofibroma/toses were negative. In summary, we describe novel NOTCH1–3 rearrangements in benign and malignant, visceral, and soft tissue GTs. © 2013 Wiley Periodicals, Inc.