A mathematical framework to determine the temporal sequence of somatic genetic events in cancer Journal Article
| Authors: | Attolini, C. S. O.; Cheng, Y. K.; Beroukhim, R.; Getz, G.; Abdel-Wahab, O.; Levine, R. L.; Mellinghoff, I. K.; Michor, F. |
| Article Title: | A mathematical framework to determine the temporal sequence of somatic genetic events in cancer |
| Abstract: | Human cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and represent promising targets for therapeutic intervention. Here we describe a computational approach, called Retracing the Evolutionary Steps in Cancer (RESIC), to deduce the temporal sequence of genetic events during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage. When applied to a dataset of 70 advanced colorectal cancers, our algorithm accurately predicts the sequence of APC, KRAS, and TP53 mutations previously defined by analyzing tumors at different stages of colon cancer formation. We further validate the method with glioblastoma and leukemia sample data and then apply it to complex integrated genomics databases, finding that high-level EGFR amplification appears to be a late event in primary glioblastomas. RESIC represents the first evolutionary mathematical approach to identify the temporal sequence of mutations driving tumorigenesis and may be useful to guide the validation of candidate genes emerging from cancer genome surveys. |
| Keywords: | leukemia; gene mutation; mutation; proto-oncogene proteins; cancer staging; genetic analysis; neoplasms; colorectal cancer; computational biology; models, biological; epidermal growth factor receptor; colonic neoplasms; algorithms; protein p53; time factors; carcinogenesis; mathematical modeling; mathematical model; cancer genetics; algorithm; disease progression; glioblastoma; tumor suppressor protein p53; genomics; ras proteins; k ras protein; apc protein; receptors, cell surface; databases, genetic; blood coagulation factors; optimization algorithm; stochastic framework; retracing the evolutionary steps in cancer |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 107 |
| Issue: | 41 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2010-10-12 |
| Start Page: | 17604 |
| End Page: | 17609 |
| Language: | English |
| DOI: | 10.1073/pnas.1009117107 |
| PUBMED: | 20864632 |
| PROVIDER: | scopus |
| PMCID: | PMC2955151 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: PNASA" - "Source: Scopus" |
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23Michor -
573Abdel-Wahab -
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