A mathematical framework to determine the temporal sequence of somatic genetic events in cancer Academic Article uri icon

Overview

MeSH Major

  • Algorithms
  • Computational Biology
  • Models, Biological
  • Neoplasms

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.

publication date

  • October 12, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2955151

Digital Object Identifier (DOI)

  • 10.1073/pnas.1009117107

PubMed ID

  • 20864632

Additional Document Info

start page

  • 17604

end page

  • 9

volume

  • 107

number

  • 41