Low frequency of HLA haplotype loss associated with loss of heterozygocity in chromosome region 6p21 in clear renal cell carcinomas

Abstract

HLA class I loss or downregulation is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes favoring tumor immune escape. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes. It has been described in different epithelial tumors that loss of heterozygosity (LOH) at chromosome region 6p21.3 is a frequent mechanism that leads to HLA haplotype loss, ranging between 40 and 50%, depending on the tumor entity analyzed. Here we have tested the frequency of LOH at 6p21 chromosome region in Renal Cell Carcinomas (RCC) of the clear cell and chromophobe subtype. A low frequency of HLA haplotype loss (6.6%) was found in clear cell RCC. These data significantly differ from those reported in other epithelial tumors. In contrast, in RCC of chromophobe subtype this frequency was 10 times higher (3 out of 5 cases analyzed). These results indicate that LOH at 6p21.3 is not a frequent mechanism that leads to HLA class I abnormalities in clear cell RCC. In addition, the chromophobe RCC subtypes differ not only in histopathological criteria but also in the frequency of LOH-mediating HLA class I alterations. These results might help to understand the significantly different biological behavior of both RCC subtypes.