Genetics of tumor metastasis 1

Published on October 29, 2015   45 min

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Other Talks in the Series: Cancer Genetics

Good morning. Robert Weinberg calling in here from the Whitehead Institute for Biomedical Research in the MIT Department of Biology, both in Cambridge, Massachusetts, USA. My talk today will be on the mechanisms of metastasis, focusing ostensibly on the genetics of metastasis, but in fact there will be great emphasis on the non-genetic mechanisms of metastasis, that is, changes in epigenetics, the control of gene transcription and how that effects the biology of cancer cells that are in the course of metastasizing.
In the first slide here, we see a description of how colorectal carcinogenesis proceeds as first enunciated, described by Kinsler and Vogelstein in 1989. And what we see here is that when one moves progressively from a normal colonic epithelial tissue towards a primary tumor, which in this case is labeled a carcinoma, one sees a series of intermediate steps which involve the accumulation of distinct genetic alterations including the loss of APC, chromosome 18 associated to tumor suppressor gene, the loss of P53, and the activation of the K-ras oncogene. And together, these operate in concert to create a primary tumor. The question is, however, what happens subsequently when the carcinoma depicted on the slide to the right actually begins to disseminate, that is send cells to distant tissues in the case of colon cancer, for example, into the liver. The question of what goes on here is critically important because of the important role of metastases in generating a large proportion of cancer associated mortality.