Chromosome Mutations and Cancer

Most tumors contain cells with chromosome mutations. For many years, geneticists argued about whether these chromosome mutations were the cause or the result of can cer. Some types of tumors are consistently associated with specific chromosome mutations, suggesting that in these cases the specific chromosome mutation played a pivotal role in the development of the cancer. However, many cancers are not associated with specific types of chromosome abnormalities, and individual gene mutations are now known to contribute to many types of cancer. Nevertheless, chromosome instability is a general feature of cancer cells, causing them to accumulate chromosome mutations, which then affect individual genes that contribute to the cancer process. Thus, chromosome mutations appear to both cause and be a result of cancer.

At least three types of chromosome rearrangements — deletions, inversions, and translocations — are associated with certain types of cancer. Deletions may result in the loss of one or more genes that normally hold cell division in check. When these so-called tumor-suppressor genes are lost, cell division is not regulated and cancer may result.

Inversions and translocations contribute to cancer in several ways. First, the chromosomal breakpoints that accompany these mutations may lie within tumor-suppressor genes, disrupting their function and leading to cell proliferation. Second, translocations and inversions may bring together sequences from two different genes, generating a fused protein that stimulates some aspect of the cancer process. Such fusions are seen in most cases of chronic myeloid leukemia, a fatal form of leukemia affecting bone-marrow cells. About 90% of patients with chronic myeloid leukemia have a reciprocal translocation between the long arm of chromosome 22 and the tip of the long arm of chromosome 9 (< Figure 9.31). This translocation produces a

— Translocation

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