Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

Maria Antonella Laginestra, Luciano Cascione, Giovanna Motta, Fabio Fuligni, Claudio Agostinelli, Maura Rossi, Maria Rosaria Sapienza, Simona Righi, Alessandro Broccoli, Valentina Indio, Federica Melle, Valentina Tabanelli, Angelica Calleri, Domenico Novero, Fabio Facchetti, Giorgio Inghirami, Elena Sabattini, Francesco Bertoni, Stefano A. Pileri

Research output: Contribution to journalArticlepeer-review

Abstract

Peripheral T-cell lymphoma not otherwise specified represents a diagnostic category comprising clinically, histologically, and molecularly heterogeneous neoplasms that are poorly understood. The genetic landscape of peripheral T-cell lymphoma not otherwise specified remains largely undefined, only a few sequencing studies having been conducted so far. In order to improve our understanding of the genetics of this neoplasm, we performed whole exome sequencing along with RNA-sequencing in a discovery set of 21 cases. According to whole exome sequencing results and mutations previously reported in other peripheral T-cell lymphomas, 137 genes were sequenced by a targeted deep approach in 71 tumor samples. In addition to epigenetic modifiers implicated in all subtypes of T-cell neoplasm (TET2, DNMT3A, KMT2D, KMT2C, SETD2), recurrent mutations of the FAT1 tumor suppressor gene were for the first time recorded in 39% of cases. Mutations of the tumor suppressor genes LATS1, STK3, ATM, TP53, and TP63 were also observed, although at a lower frequency. Patients with FAT1 mutations showed inferior overall survival compared to those with wild-type FAT1. Although peripheral T-cell lymphoma not otherwise specified remains a broad category also on molecular grounds, the present study highlights that FAT1 mutations occur in a significant proportion of cases, being provided with both pathogenetic and prognostic impact.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalModern Pathology
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 1 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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