Absolute quantification of somatic DNA alterations in human cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-05

AUTHORS

Scott L Carter, Kristian Cibulskis, Elena Helman, Aaron McKenna, Hui Shen, Travis Zack, Peter W Laird, Robert C Onofrio, Wendy Winckler, Barbara A Weir, Rameen Beroukhim, David Pellman, Douglas A Levine, Eric S Lander, Matthew Meyerson, Gad Getz

ABSTRACT

We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity. More... »

PAGES

413

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.2203

DOI

http://dx.doi.org/10.1038/nbt.2203

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1010515132

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22544022


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