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

Int J Cancer. 1999 Sep 24;83(1):91-7. doi: 10.1002/(sici)1097-0215(19990924)83:1<91::aid-ijc17>3.0.co;2-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Chromosomes, Human, Pair 6
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Disease Progression
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen / immunology
  • HLA-B Antigens / immunology
  • HLA-B7 Antigen / immunology
  • Haplotypes*
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / immunology
  • Loss of Heterozygosity*
  • Melanoma / genetics
  • Melanoma / immunology
  • Microsatellite Repeats
  • Models, Genetic

Substances

  • Antibodies, Monoclonal
  • HLA Antigens
  • HLA-A Antigens
  • HLA-A2 Antigen
  • HLA-B Antigens
  • HLA-B7 Antigen
  • HLA-Bw4 antigen