Exomic Analysis of Myxoid Liposarcomas, Synovial Sarcomas, and Osteosarcomas

Overview

Journal Genes Chromosomes Cancer

Specialties Molecular Biology
Oncology

Date 2013 Nov 6

PMID 24190505

Citations 54

Authors

Christine G Joseph

Heejung Hwang

Yuchen Jiao

Laura D Wood

Isaac Kinde

Jian Wu

Nils Mandahl

Jinyong Luo

Ralph H Hruban

Luis A Diaz Jr

Tong-Chuan He

Bert Vogelstein

Kenneth W Kinzler

Fredrik Mertens

Nickolas Papadopoulos

Affiliations

Soon will be listed here.

Abstract

Bone and soft tissue sarcomas are a group of histologically heterogeneous and relatively uncommon tumors. To explore their genetic origins, we sequenced the exomes of 13 osteosarcomas, eight myxoid liposarcomas (MLPS), and seven synovial sarcomas (SYN). These tumors had few genetic alterations (median of 10.8). Nevertheless, clear examples of driver gene mutations were observed, including canonical mutations in TP53, PIK3CA, SETD2, AKT1, and subclonal mutation in FBXW7. Of particular interest were mutations in H3F3A, encoding the variant histone H3.3. Mutations in this gene have only been previously observed in gliomas. Loss of heterozygosity of exomic regions was extensive in osteosarcomas but rare in SYN and MLPS. These results provide intriguing nucleotide-level information on these relatively uncommon neoplasms and highlight pathways that help explain their pathogenesis.

Citing Articles

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SETD2 loss-of-function uniquely sensitizes cells to epigenetic targeting of NSD1-directed H3K36 methylation.

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