Identification of frequent BRAF copy number gain and alterations of RAF genes in chinese prostate cancer

Abstract

We recently found that TMPRSS2:ERG fusion genes and PTEN loss, which are common in Western prostate cancers are infrequent in Chinese cases. As previous studies indicated a higher frequency of RAS and BRAF mutation rates in Eastern Asian than in Western prostate cancers and fusion genes involving the RAF family genes BRAF and RAF1 were recently identified in prostate cancer in the American population, we investigated BRAF and RAF1 alterations in Chinese prostate cancer. Using fluorescence in situ hybridization, we found that BRAF was truncated in five of 200 informative Chinese cases (2.5%) and that RAF1 was truncated in three of 204 informative cases (1.5%) and genomic rearrangements of these genes were significantly correlated with high Gleason scores (>7; P < 0.01) and have a trend to appear in high clinical stage disease. A high frequency of BRAF and RAF1 copy number gain was found (29 and 15%, respectively). BRAF copy number gain in Chinese cancers was significantly higher than in UK cases (9.2%)(P < 0.001) and correlated with a number of clinical parameters. High-level expression of BRAF was found by immunohistochemistry in Chinese cancer samples compared with adjacent nonmalignant epithelial cells, which was correlated with high BRAF copy number. We also identified KRAS codon 12 mutations in three of 96 Chinese cases, no BRAF V600E mutations were observed. Our finding suggests that the activation of the RAS/RAF/MEK/ERK pathway may be frequent in Chinese prostate cancer, with RAF gene copy number gain potentially being the main contributor.