title: Distribution of HLA class I altered phenotypes in colorectal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21.
abstract: HLA class I loss or down-regulation is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes, and thus favor tumor immune escape. Multiple mechanisms are responsible for these HLA class I alterations. In different epithelial tumors, loss of heterozygosity (LOH) at chromosome region 6p21.3, leading to HLA haplotype loss, occurs in 6-50% of all cases depending on the tumor entity. In this paper we report the frequency of LOH at 6p21 in 95 colorectal carcinomas (CRC) previously analyzed for altered HLA class I expression with immunohistological techniques. We used PCR microsatellite amplification of selected STR markers located on Chromosome 6 to identify LOH with DNA from microdissected tumor tissues and the surrounding stroma. Sequence-specific oligonucleotide analysis was performed in microdissected stroma and tumor cells for HLA typing, and to detect HLA haplotype loss. A high frequency (40%) of HLA haplotype loss was found in CRC. Eight tumors showed microsatellite instability. We sometimes observed two or more mechanisms responsible for HLA alteration within the same HLA-altered phenotype, such as LOH and HLA class I total loss. In 25 tumors (26%) no HLA class I alteration could be identified. These data are potentially relevant for CRC patients undergoing T-cell-based immunotherapy.
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avd. Fuerzas Armadas 2, 18014 Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Maleno
authors.forename: Carmen Maria
authors.initials: CM
authors.lastname: Cabrera
authors.forename: Teresa
authors.initials: T
authors.lastname: Cabrera
authors.forename: Laura
authors.initials: L
authors.lastname: Paco
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Antonia
authors.initials: A
authors.lastname: Collado
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrón
authors.forename: Federico
authors.initials: F
authors.lastname: Garrido
mesh_terms: D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000032:analysis*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010641:Phenotype
chemical_list: D006680:HLA Antigens