Michor F, Iwasa Y, Rajagopalan H, Lengauer C, Nowak MA. 2004. Linear model of colon cancer initiation. Cell cycle (Georgetown, Tex.). 3(3):358-62. Pubmed: 14726709


Cancer results if regulatory mechanisms of cell birth and death are disrupted. Colorectal tumorigenesis is initiated by somatic or inherited mutations in the APC tumor suppressor gene pathway. Several additional genetic hits in other tumor suppressor genes and oncogenes drive the progression from polyps to malignant, invasive cancer. The majority of colorectal cancers present chromosomal instability, CIN, which is caused by mutations in genes that are required to maintain chromosomal stability. A major question in cancer genetics is whether CIN is an early event and thus a driving force of tumor progression. We present a new mathematical model of colon cancer initiation assuming a linear flow from stem cells to differentiated cells to apoptosis. We study the consequences of mutations in different cell types and calculate the conditions for CIN to precede APC inactivation. We find that early emergence of CIN is very likely in colorectal tumorigenesis.

Related Faculty

Photo of Franziska Michor

Franziska Michor uses the tools of theoretical evolutionary biology, applied mathematics, statistics, and computational biology to address important questions in cancer research.

Search Menu