title: Chromosomal mechanisms in the initiation of human familial mixed cancers.
abstract: A strong case for a genetic diathesis in human cancer can be made through the analysis of familial aggregations of mixed tumor types. This is particularly true for childhood cancers which have a very low incidence when compared to that of adult cancer and for which common environmental factors appear to play little etiological role. Here are described studies designed to apply molecular genetic analysis toward defining the lesions which predispose to human cancer. We found that the clinically associated tumors retinoblastoma and osteosarcoma share a pathogenetic mechanism entailing aberrant chromosomal segregation events during mitosis which lead to tumor cells homozygous for recessive mutant alleles at the RB1 locus on human chromosome 13 band q14. These results suggest that a rational explanation for the sequential occurrence in these children of two different tumor types is the initial inheritance of a predisposing recessive mutation with broad but specific tissue activity.
authors.affiliation: Ludwig Institute for Cancer Research, Montreal, Quebec, Canada.
authors.forename: W K
authors.initials: WK
authors.lastname: Cavenee
mesh_terms: D002869:Chromosome Aberrations; D004198:Disease Susceptibility; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics; D012175:Retinoblastoma / Q000235:genetics