Multistep carcinogenesis

The development of cancer is a multi-step process characterized by repeated cellular insults resulting in the accumulation of mutations. The steps involved in the development of colorectal cancer have been particularly well characterized (see figure). Single mutations (e.g. APC) can lead to benign cellular proliferation (familial polyposis coli) that predisposes to the development of malignancy. Mutations in DNA repair genes (e.g. MMR—mis-match repair) speed up this process of mutation accumulation.

p53 Other changes ?

DCC DPC4

APC DNA hypomethylation K-ras JV18 ?

DCC DPC4

APC DNA hypomethylation K-ras JV18 ?

Normal epithelium

Dysplastic

Early adenoma

Intermediate adenoma

Late adenoma

Carcinoma

Metastasis

MMR deficiency

MMR deficiency

Genetic alterations associated with colorectal carcinogenesis. Mutation frequencies in MMR-deficient cells are two to three times higher than in normal cells—such MMR mutations are found in > 70% of hereditary non-polyposis colorectal cancer (HNPCC) cases and > 65% of sporadic colorectal cancers exhibiting micro-satellite instability.These cases account for 15-17% of total colorectal cancers. (Adapted from Kinzler and Vogelstein).

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment