Subtype-specific genomic alterations define new targets for soft tissue sarcoma therapy
Name
Lander_Subtype-specific.pdf
Size
2.74 MB
Format
Adobe PDF
Checksum (MD5)
f12e53e2042f4c4b87c3857686590396
Author(s)
Lander, Eric S.
Meyerson, Matthew L.
Date Issued
July 2010
Journal
Nature Genetics
Publisher
Nature Publishing Group
Citation
Jordi Barretina et al. "Subtype-specific genomic alterations define new targets for soft tissue sarcoma therapy" Nature Genetics 42, 715–721(2010).
Version
Author's final manuscript
Abstract
Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States1, show remarkable histologic diversity, with more than 50 recognized subtypes2. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.
Description
2011 February 1
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/ng.619
