TAILIEUCHUNG - báo cáo khoa học: " Environmental exposures and mutational patterns of cancer genomes"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Environmental exposures and mutational patterns of cancer genomes | Pfeifer Genome Medicine 2010 2 54 http content 2 8 54 w Genome Medicine MINIREVIEW L__ Environmental exposures and mutational patterns of cancer genomes Gerd P Pfeifer Abstract The etiology of most human cancers is unknown. Genetic inheritance and environmental factors are thought to have major roles and for some types of cancer exposure to carcinogens is a proven mechanism leading to tumorigenesis. Sequencing of entire cancer genomes has not only begun to provide clues regarding functionally relevant mutations but has also paved the way towards understanding the initial exposures leading to DNA damage repair and eventually to mutation of specific sequences within a cancer genome. Two recent studies of melanoma and small cell lung cancer exemplify what type of information can be gained from cancer genome sequencing. Origins of human cancer The origins of human cancers have environmental and hereditary components. Germline mutations of tumor suppressor genes found in cancer predisposition syndromes are prominent examples of inheritance and include well known tumor suppressor genes such as the retinoblastoma gene RB TP53 the breast cancer genes BRCA1 and BRCA2 the adenomatous polyposis coli gene APC the mismatch repair genes MLH1 and MSH2 and a few others. Although mutations in these genes are very rare in the general population they confer a high risk for developing the disease. Mutations in this group of genes account for only a small fraction of the excess cancer incidence in familial cancer. For some common cancers with significant aspects of heritability such as prostate cancer highly penetrant susceptibility genes are still unknown. For these reasons attention has now shifted towards ascribing much of the observed familial cancer risk to polygenic models of predisposition in which variant alleles each conferring a small added risk Correspondence gpfeifer@ Department of Cancer Biology Beckman Research Institute City of Hope .

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