Network-based stratification of tumor mutations.

TitleNetwork-based stratification of tumor mutations.
Publication TypeJournal Article
Year of Publication2013
AuthorsHofree M, Shen JP, Carter H, Gross A, Ideker T
JournalNat Methods
Volume10
Issue11
Pagination1108-15
Date Published2013 Nov
ISSN1548-7105
KeywordsHumans, Mutation, Neoplasms
Abstract

Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence.

DOI10.1038/nmeth.2651
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/24037242?dopt=Abstract
Alternate JournalNat. Methods
PubMed ID24037242
PubMed Central IDPMC3866081
Grant ListP30 CA023100 / CA / NCI NIH HHS / United States
P41 GM103504 / GM / NIGMS NIH HHS / United States
P41 GM103504 / GM / NIGMS NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology