TAILIEUCHUNG - Chapter 079. Cancer Genetics (Part 9)

Chromosomal Instability in Solid Tumors Solid tumors are generally highly aneuploid, containing an abnormal number of chromosomes; these chromosomes also exhibit structural alterations such as translocations, deletions, and amplifications. Again, colon cancer has proven to be a particularly useful model for the study of chromosomal instability (CIN). As described above, some familial cases are characterized by the presence of MIN. Interestingly, MIN and CIN appear to be mutually exclusive in colon cancer, suggesting that they represent alternative mechanisms for the generation of a mutator phenotype in this cancer (Fig. 79-2). Other cancer types rarely exhibit MIN but almost always. | Chapter 079. Cancer Genetics Part 9 Chromosomal Instability in Solid Tumors Solid tumors are generally highly aneuploid containing an abnormal number of chromosomes these chromosomes also exhibit structural alterations such as translocations deletions and amplifications. Again colon cancer has proven to be a particularly useful model for the study of chromosomal instability CIN . As described above some familial cases are characterized by the presence of MIN. Interestingly MIN and CIN appear to be mutually exclusive in colon cancer suggesting that they represent alternative mechanisms for the generation of a mutator phenotype in this cancer Fig. 79-2 . Other cancer types rarely exhibit MIN but almost always exhibit CIN. Normal cells possess several cell cycle checkpoints often defined as quality-control requirements that have to be met before subsequent events are allowed to take place. The spindle checkpoint which ensures proper chromosome attachment to the mitotic spindle before allowing the sister chromatids to separate has been shown to be deficient in certain cancers. The genes that when mutated may cause CIN have in general not yet been identified although a few candidates mutated in a small number of tumors have been discovered. The identification of the cause of CIN in tumors will likely be a formidable task considering that several hundred genes are thought to control the mitotic checkpoint and other cellular processes assuring proper chromosome segregation. Regardless of the mechanisms underlying CIN the measurement of the number of chromosomal alterations present in tumors is now possible with both cytogenetic and molecular techniques and several studies have shown that this information can be useful for prognostic purposes. Viruses in Human Cancer Certain human malignancies are associated with viruses. Examples include Burkitt s lymphoma Epstein-Barr virus hepatocellular carcinoma hepatitis virus cervical cancer human papillomavirus HPV and T cell .

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