Truncation of BRAF and Raf1 in prostate cancer in China.

Abstract

77 Background: Chromosome translocations and fusion genes have been identified as common events in carcinomas in recent years and TMPRSS2:ERG fusions have been found in about half of human prostate cancers. However, by genome-wide analysis of Chinese prostate cancer cases, we found that certain genomic alterations, commonly identified in prostate cancer samples from the Western countries, occurred at a very low frequency in China, including the fusion of TMPRSS2:ERG. In 2010, recurrent fusion genes involving the RAF family gene BRAF and Raf1 were identified (Palanisamy et al, Nature Med. 16:793). Although the frequency of fusions involving BRAF and Raf1 are at a much lower frequency than fusion of TMPRSS2:ERG, BRAF and Raf1 are drugable, making them potential therapeutic targets. As the TMPRSS2:ERG fusion is infrequent in Chinese prostate cancers, we investigated if fusions involving BRAF and Raf1 occur at a higher frequency in prostate cancer in China than in Western countries. Methods: We used the fluorescence in situ hybridization signal split apart approach on prostate cancer samples made into tissue microarrays to detect the frequency of BRAF and Raf1 truncations. Three BAC probes on each side (5’ and 3’) of the two genes were labeled differentially using biotin and digoxigenin and subsequentially detected as red and green fluorescent signals, respectively. Results: We found that BRAF was truncated in four (two split signals, one 5’ deletions and one 3’ deletions) of the 193 informative cases (2.07%) and RAFaf1 (two 5’ deletions and one split signals) was truncated in three of 201 informative cases (1.49%). Although in some cases, three or four copies of these genes were detected, extensive copy number gain caused by amplification was not detected. Conclusions: These results indicate that truncations and potentially fusion of BRAF and Raf1 exist in Chinese prostate cancer, but at a similar low frequency as found in the Western samples (6/349 for BRAF and 4/450 for Raf1). Further studies are required to confirm the functional consequence of these truncations and to evaluate the therapeutic value of targeting these genes in this sub-group of prostate cancers.