beta(2)-microglobulin gene mutation is not a common mechanism of HLA classI total loss in human tumors

One hundred and sixty-two tumor samples were analyzed for HLA class I expre ssion using immunohistological techniques. HLA class I total loss (phenotyp e no. I) was detected in 31 cases (19%), comprising 20 colorectal, 3 laryng eal, and 2 bladder carcinomas and 6 melanomas. Twenty-one cases were select ed for molecular analysis due to a higher proportion of tumor cells versus stroma cells (75%). We investigated whether beta(2)-microglobulin mutation was responsible for HLA downregulation. Single-strand conformation polymorp hism and sequencing analysis of DNA samples was performed. Alterations were detected only in melanomas M78 (a point mutation in the initiation ATG seq uence), M79 (a mutation in codon 31 producing a stop codon), and M34 (a TTC T deletion introducing a termination codon signal). We found no beta(2)-mic roglobulin gene mutation in the other 18 samples. Loss of heterozygosity in 15q close to the beta(2)-microglobulin gene was found in 5 cases. We concl ude that HLA class I total loss can frequently occur without beta(2)-microg lobulin gene mutations.