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 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.
Jiménez
P
P
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Cantón
J
J
Collado
A
A
Cabrera
T
T
Serrano
A
A
Real
L M
LM
García
A
A
Ruiz-Cabello
F
F
Garrido
F
F
D000911:Antibodies, Monoclonal; D002896:Chromosomes, Human, Pair 6; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015793:HLA-B7 Antigen / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000276:immunology; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000235:genetics / Q000276:immunology; D018895:Microsatellite Repeats; D008957:Models, Genetic
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D015793:HLA-B7 Antigen; C042388:HLA-Bw4 antigen