Chromosome loss is the most frequent mechanism contributing to HLA haplotype loss in human tumors

Loss of heterozygosity (LOH) in the short arm of chromosome 6 (6p) was dete cted in samples obtained from colon (13.8%), larynx (17.6%) and melanoma(15 .3%) tumors. The parallel study of HLA-antigen expression in tumor tissues using locus- and polymorphic-specific antibodies in combination with LOH mi crosatellite analysis on 6p allowed us to establish that LOH in chromosome 6 is a representative phenomenon in most tumor cells present in a given tum or tissue. In most cases, specific HLA alleles had been lost in a predomina nt population of tumor cells, indicating that LOH is a non-irrelevant mutat ion that probably confers a selective advantage for survival of the mutant cell. We also demonstrate that LOH frequently occurred through chromosome l oss rather than somatic recombination. LOH at all loci studied on the p and q arms of chromosome 6 was observed in at least 56.2% (9/17) cases. This H LA-associated microsatellite analysis was a useful tool for classifying tum ors as LOH-positive or -negative, and therefore to consider a patient as a potential non-responder or responder in a vaccination trial. (C) 1999 Wiley -Liss, Inc.