SCIENTIFIC ADVANCES

Mathematical Modeling of Cancer Oncogenesis

Drs. Zhang and Simon used age-incidence data to try to determine the number of rate-limiting events in breast cancer oncogenesis. They developed a model that incorporated the age-dependent dynamics of breast epithelium and clonal expansion of intermediate cells without the full complement of mutations required for an invasive tumor. They found that it was unlikely that there are more than three rate-limiting events in breast cancer oncogenesis occurring at a rate characteristic of point mutations in normal mammalian cells. The initial set of two or three mutational events appears to destabilize the genome and puts in place a process that almost inevitably leads to an invasive tumor. They also analyzed similar age-incidence data for breast cancer in BRCA1 and BRCA2 mutation carriers and found results consistent with those for sporadic cases.

Simon R, Zhang X. On the dynamics of breast tumor development in women carrying germline BRCA1 and BRCA2 mutations. Int J Cancer2008:122;1916–7.
http://www.ncbi.nlm.nih.gov/pubmed/18098285