Loss of heterozygosity in stages of malignancy.

The determination and comparison of genotypic combinations at genomic loci in constitutional and tumor tissues from patients with various types of cancer have defined the chromosomal locations of loci in which recessive mutations play a role in disease development. The predisposing nature of some of these mutant alleles is exemplified by studies of retinoblastoma and osteogenic sarcoma, two clinically associated diseases that share a pathogenetically causal predisposition mapping to 13q14. Genomic alteration of chromosome 10 is apparent in glioblastomas and mixed tumors of glioblastoma/astrocytoma grade III but not in homogeneous astrocytoma grades II or III; this suggests the definition of a locus involved in tumor progression and, perhaps, an approach to molecular genetic staging of tumors.