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1. The Somatic-Mutation Theory of Cancer
Pages 1-7

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From page 1...
... 110 Other examples of chromosomal aberrations assay elated with neoplasia include a chromosome 3:S translocation with hereditary renal cell carcinoma, 40 a chromosome 13 de le t i on wi th re t inob las tome, 64 and a de let ion in chromes ome 11 with Wilms' tumor. In a report from the National Wilms' Tumor Study, Breslow and Beckwith29 suggested that the proportion of Wilms' tumors due to inherited mutation may be substantially smaller than previously estimated.
From page 2...
... Recent ly , insertion of viral promoters has been shown to cause transformation in cell cultures by enhanced transcription of viral or endogenous oncogenes.3b,91 EndogenOgs5 onc5Ogenes have been mapped on specific human chromosomes, ~ and there is evidence that reciprocal translocations may bring these genes under different promotional control.62 Thus, chromosomal rearrangements (observed by using cytogenetic techniques) and small-ecale transposition events (that can be detected only genetically)
From page 3...
... Stable and nonstable genetic features of the ~ omplex are used to assess germinal mutation and somatic gene expression that results from transposition of a duplicate regulatory locus in w+. Preliminary evidence derived from the few carcinogens tested suggests that mutagenic carcinogens have an influence on supposed transpositions, but this phenol enon is unrelated to a carcinogen's mutagenic potency.
From page 4...
... Because no specific experimental factor accurately predicts human carcinogenicity, Squire proposed ranking potential carcinogens according to several factors, including genotoxicity tests. There are two principal reasons why some chemical carcinogens are not detected in mutagenicity tests.
From page 5...
... For example, malignancy can be suppressed in natural ly occurring human cancers by fus ion of cancer cel Is to normal human fibroblasts, differentiating epithelial keratinocytes, and cancer cells of different somatic cell origin. But suppression has not yet been specifically linked either with a cancer cell of a particular origin or with a type of nonmalignant cell to which the cancer cell is fused.
From page 6...
... McKusick}6 listed approximately 30 human cancers that may be inherited in a dominant fashion. These account for approximately I: of all human cancers in the United States.63 The total number of human cancer genes remains a matter of speculation; Moolgavkar and Knudson 0 suggested that there may be 100-200, whereas recent hybridization data between viral or human oncogenes and human DNA imply a range of only 10-20.25 However, the sensitivity of nucleic acid hybridization techniques is probably not so great that all cancer genes can be detected definitively.
From page 7...
... Although some pi rsone are at tremendous risk, only a minute fraction of human cancers are in this category. The second category includes cancers for which a genetic predispos ition leads to risks approximately 10-100 times higher than that in the general populat ion.


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