Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets. Academic Article uri icon

Overview

abstract

  • The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analysis of 2,138 sarcomas representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations are in cell cycle control and TP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations include TERT amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varies between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response.

authors

publication date

  • June 15, 2022

Research

keywords

  • Bone Neoplasms
  • Osteosarcoma
  • Sarcoma
  • Soft Tissue Neoplasms

Identity

PubMed Central ID

  • PMC9200818

Scopus Document Identifier

  • 85132079935

Digital Object Identifier (DOI)

  • 10.1186/gb-2004-5-10-r80

PubMed ID

  • 35705560

Additional Document Info

volume

  • 13

issue

  • 1