Absolute quantification of somatic DNA alterations in human cancer Journal Article
| Authors: | Carter, S. L.; Cibulskis, K.; Helman, E.; McKenna, A.; Shen, H.; Zack, T.; Laird, P. W.; Onofrio, R. C.; Winckler, W.; Weir, B. A.; Beroukhim, R.; Pellman, D.; Levine, D. A.; Lander, E. S.; Meyerson, M.; Getz, G. |
| Article Title: | Absolute quantification of somatic DNA alterations in human cancer |
| 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. © 2012 Nature America, All Right Reserved. |
| Keywords: | gene mutation; gene sequence; human cell; somatic mutation; flow cytometry; neoplasm; neoplasms; ovarian neoplasms; allele; genes; alleles; cell line, tumor; biotechnology; protein p53; cancer genetics; homozygosity; tumor suppressor gene; dna; tumors; disease progression; cancer cell; ovary carcinoma; homozygote; tumor suppressor protein p53; neurofibromin 1; dna mutational analysis; ovarian carcinoma; gene dosage; point mutation; tumor suppressor genes; cyclin-dependent kinases; genetic techniques; cell separation; aneuploidy; dna determination; diseases; genome, human; genetic heterogeneity; human cancer; cancer genome; malignant cells; tumor progressions; ploidy; ploidies; absolute quantification; exome; aneuploids; genome doubling; statistical sensitivity |
| Journal Title: | Nature Biotechnology |
| Volume: | 30 |
| Issue: | 5 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-04-29 |
| Start Page: | 413 |
| End Page: | 421 |
| Language: | English |
| DOI: | 10.1038/nbt.2203 |
| PROVIDER: | scopus |
| PUBMED: | 22544022 |
| PMCID: | PMC4383288 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 June 2012" - "CODEN: NABIF" - "Source: Scopus" |
