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

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Abstract
Loss of heterozygosity (LOH) in the short arm of chromosome 6 (6p) was detected 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 microsatellite analysis on 6p allowed us to establish that LOH in chromosome 6 is a representative phenomenon in most tumor cells present in a given tumor tissue. In most cases, specific HLA alleles had been lost in a predominant population of tumor cells, indicating that LOH is a non‐irrelevant mutation that probably confers a selective advantage for survival of the mutant cell. We also demonstrate that LOH frequently occurred through chromosome loss 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 HLA‐associated microsatellite analysis was a useful tool for classifying tumors as LOH‐positive or ‐negative, and therefore to consider a patient as a potential non‐responder or responder in a vaccination trial. Int. J. Cancer 83:91–97, 1999.