Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites
(FISH) on interphase cells and isolated DNA fibers. Total loss of HLA-A expres- sion was found in 60% of the extranodal cases and in 10% of the nodal cases (P < .01), whereas loss of HLA-DR ex- pression was found in 56% and 5%, respectively (P < .01). This was accom- panied by extensive loss of heterozygos- ity within the HLA region in the extran- odal DLCLs. In 3 cases, retention of heterozygosity for D6S1666 in the class II region suggested a homozygous dele- tion. This finding was confirmed by inter- phase FISH that showed homozygous deletions in the class II genes in 11 of the 18 extranodal lymphomas but in none of the 7 nodal DLCLs (P < .001). Mapping by fiber FISH showed variable deletions that always included HLA-DQ and HLA-DR genes. Hemizygous dele- tions and mitotic recombinations often involving all HLA genes were found in 13 of 18 extranodal and 2 of 7 nodal lymphomas. In conclusion, a structural loss of HLA class I and II expression might help the B-cell lymphoma cells to escape from immune attack. (Blood. 2000;96:3569-3577)
Published in 2000.