Loss of heterozygosity at autosomal and X-linked loci during tumor progression in a patient with melanoma.
Restriction fragment length polymorphisms at 61 autosomal and 7 X-linked loci were screened for heterozygosity in cell lines derived from 6 independent metastases and autologous B-cells from a patient with melanoma. Segregations resulting in the loss of heterozygosity were detected in the tumor cells at 8 of 16 autosomes with at least 1 informative locus and at the 3 informative X-linked loci. With a single exception, karyotypic abnormalities were not detected in the region of loci where loss of heterozygosity had been detected. Three patterns of loss were identified: unique segregations in cells from a single metastasis; segregation of the same alleles in different subsets of metastases; and identical segregations in all 6 metastases. The monoclonal derivation of the 6 metastases is supported by the inactivation of the same X-chromosome and the presence of identical segregation at loci on chromosomes 9 and X. Analysis of the patterns of segregation in the metastatic tumor cells permitted the development of a genealogy of tumor progression in this patient and the development of a model of tumor progression which describes the accumulation of selectively neutral and advantageous segregations in metastatic tumor cells.
D000008:Abdominal Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D000368:Aged; D000782:Aneuploidy; D001402:B-Lymphocytes / Q000032:analysis; D002460:Cell Line; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000473:pathology; D004303:Dosage Compensation, Genetic; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D008954:Models, Biological; D012150:Polymorphism, Restriction Fragment Length; D012641:Selection, Genetic; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary
D005819:Genetic Markers