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Development of cancer was proposed in 1971 to depend on at least two mutational events. In what became known as the Knudson two-hit hypothesis, an inherited, germ-line mutation in a tumor suppressor gene would cause cancer only if another mutation event occurred later in the organism's life, inactivating the other allele of that tumor ...
Hereditary cancers are primarily caused by an inherited genetic defect. A cancer syndrome or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predisposes the affected individuals to the development of cancers and may also cause the early onset of these cancers. Although cancer syndromes ...
If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they predispose the cell to cancer and are termed oncogenes. Usually, multiple oncogenes, along with mutated apoptotic or tumor suppressor genes, act in concert to cause cancer. Since the 1970s, dozens of oncogenes have been identified in ...
These genes are involved in pathways known to contribute to cancer pathogenesis, but before this study most would not have been candidates for targeted gene therapy. This analysis validated the approach of whole cancer genome sequencing in identifying somatic mutations and the importance of parallel sequencing of normal and tumor cell genomes.
Hereditary non-polyposis colon cancer, also known as Lynch syndrome, is an autosomal dominant cancer syndrome that increases the risk of colorectal cancer. It is caused by genetic mutations in DNA mismatch repair (MMR) genes, notably MLH1, MSH2, MSH6 and PMS2. In addition to colorectal cancer many other cancers are increased in frequency.
One underlying commonality in cancers is genetic mutation, acquired either by inheritance, or, more commonly, by mutations in one's somatic DNA over time. The mutations considered important in cancers are those that alter protein coding genes (the exome). As Vogelstein et al. point out, a typical tumor contains two to eight exome "driver gene ...
Other carcinogens may cause cancer through a variety of mechanisms without producing mutations, such as tumour promotion, immunosuppression that reduces the ability to fight cancer cells or pathogens that can cause cancer, disruption of the endocrine system (e.g. in breast cancer), tissue-specific toxicity, and inflammation (e.g. in colorectal ...
In whole genome sequencing of different types of cancers, large numbers of mutations were found in two breast cancers (about 20,000 point mutations [43]), 25 melanomas (9,000 to 333,000 point mutations [44]) and a lung cancer (50,000 point mutations and 54,000 small additions and deletions [45]). Genome instability is also referred to as an ...
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