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  • Title: Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.
    Author: Hansen MF, Koufos A, Gallie BL, Phillips RA, Fodstad O, Brøgger A, Gedde-Dahl T, Cavenee WK.
    Journal: Proc Natl Acad Sci U S A; 1985 Sep; 82(18):6216-20. PubMed ID: 2994066.
    Abstract:
    Survivors of the heritable form of retinoblastoma subsequently develop second primary osteosarcomas at substantially greater frequency than either the general population or survivors of nonheritable retinoblastoma. Here we present molecular genetic evidence that the development of these two disparate tumor types involves specific somatic loss of constitutional heterozygosity for the region of human chromosome 13 that includes the RB1 locus. Similar events occur during the genesis of nonheritable osteosarcoma but not in several other embryonal tumors or sarcomas. These findings suggest that a conceptual approach toward defining the number of genes whose recessive mutant forms predispose to cancer is the molecular genetic analysis of clinically associated tumor types. They also suggest that the molecular basis of mixed cancer families may be the differential expression of a single pleiotropic recessive mutation by tissue specific mitotic segregation abnormalities.
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