The genetics of childhood cancer.
Two classes of genes are apparently critical in the origin of the cancers of children. One class, that of oncogenes, acts by virtue of abnormal or elevated activity. It is operative primarily in leukemias and lymphomas. There is no evidence yet that genetic predisposition to these neoplasms can be imparted by oncogene mutations in the germline. However, there are conditions that predispose to these tumors, primarily through excessive chromosomal breakage and rearrangement. The other class, that of anti-oncogenes, is recessive in oncogenesis; cancer results when both normal copies have been mutated or deleted. Some persons carry one such mutation in the germline and are highly susceptible to tumor because only one somatic event is necessary. Some children, even though carrying no such mutation in the germline, can acquire tumor as a result of two somatic events. Most solid tumors in children seem to involve initiation through the loss of both copies of an anti-oncogene.
Knudson
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AG
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes; D011995:Recombination, Genetic; D012307:Risk Factors; D014178:Translocation, Genetic