Document Detail

A mathematical framework to determine the temporal sequence of somatic genetic events in cancer.
MedLine Citation:
PMID:  20864632     Owner:  NLM     Status:  MEDLINE    
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.
Camille Stephan-Otto Attolini; Yu-Kang Cheng; Rameen Beroukhim; Gad Getz; Omar Abdel-Wahab; Ross L Levine; Ingo K Mellinghoff; Franziska Michor
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-09-23
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-13     Completed Date:  2010-11-22     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17604-9     Citation Subset:  IM    
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MeSH Terms
Blood Coagulation Factors / genetics
Colonic Neoplasms / genetics
Computational Biology / methods*
Databases, Genetic
Disease Progression
Genomics / methods
Glioblastoma / genetics
Models, Biological*
Mutation / genetics
Neoplasms / genetics*
Proto-Oncogene Proteins / genetics
Receptors, Cell Surface / genetics
Time Factors
Tumor Suppressor Protein p53 / genetics
ras Proteins / genetics
Grant Support
Reg. No./Substance:
0/Blood Coagulation Factors; 0/KRAS protein, human; 0/Proto-Oncogene Proteins; 0/Receptors, Cell Surface; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/activated protein C receptor; EC Proteins
Comment In:
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):E15; author reply E16   [PMID:  21239682 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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