APY248 Genetics

APY248 Genetics - Genetics of Cancer Cancer is a genetic...

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Unformatted text preview: Genetics of Cancer Cancer is a genetic disease Cancers result from mutations in the genes that regulate cell growth. DNA damage increases the risk of developing cancer. Familial cancer syndromes are due to mutations in genes affecting DNA repair or genes that regulate cell growth. Experimental approaches Cytogenetics Chromosomes (metaphase) from dividing tumor cells are spread onto glass slides and stained with DNA dyes. Can only detect gross changes (chromosome gain, loss or rearragment) Insensitive and applicable to only a limited number of cancers. However, have been critical in pointing the way toward specific cancer genes. Experimental approaches FISH (Fluorescent in situ Hybridization) DNA from interphase tumor cells are spread onto glass slides. Hybridization with specific DNA sequences, labeled with fluorescent dyes. Detects translocation, loss or gain (amplification) of gene in question. Sensitive but applicable only to enquiry regarding the specific gene(s) in question. Experimental approaches PCR DNA extracted from tumor cells and PCR- amplified with gene-specific probes. Detects translocation. In combination with sequencing can identify point mutations in the gene in question. Highly sensitive but applicable only to enquiry regarding the specific gene(s) in question. Experimental approaches Viral carcinogenesis (Retrovirus) Identification of the gene activated by insertional mutagenesis (slow-transforming viruses). Identification of the transduced cellular gene for acutely transforming retroviruses. Experiment of nature. Requires independent confirmation but extremely rich source for identification of cellular genes involved in cancer. Does not identify tumor suppressor genes. Experimental approaches Viral carcinogenesis (DNA viruses) Identification of the proteins that are inactivated by interaction with viral proteins. Experiment of nature. Requires identification of the protein product (easier now) and testing in other model systems to determine function. Generally identifies tumor suppressor genes. Cancers are associated with mutations that activate proteins that stimulate cell growth The Ph 1 chromosome Chronic myelogenous leukemia (CML) is a malignant disorder of blood cells that ultimately evolves into acute leukemia, which is rapidly fatal. The Ph 1 chromosome In 1960, Nowell demonstrated that the leukemic cells from CML patients had a characteristic chromosomal abnormality, t(9:22). This was not present in the patients normal cells. Thus, the Ph 1 chromosome is an acquired genetic abnormality. This was the first example of a genetic abnormality consistently associated with cancer. Retroviral Oncogenesis Simple RNA viruses that transform cells by: Integrating into DNA and activating transcription of a growth regulating gene (proto-oncogene). Slow transformation....
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APY248 Genetics - Genetics of Cancer Cancer is a genetic...

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