Identification of distinct regions of allelic loss on chromosome 13q in nasopharyngeal cancer from paraffin embedded tissues

Our main purpose was to identify tumor suppressor gene loci on chromosome 1 3 responsible for nasopharyngeal cancer (NPC) development by analyzing loss of heterozygosity (LOH) and RE protein expression in paraffin embedded tis sues. Normal and tumor DNA were extracted from microdissected samples, and their whole genomes were amplified using degenerate oligonucleotide primers . The polymerase chain reaction (PCR) products were analyzed by repeated am plification using primers derived from 16 microsatellite regions spanning t he long arm of this chromosome. Among 50 informative cases, LOH was observe d in 44 tumors. Thirty-one tumors displayed partial loss and provided an in formative basis for detailed deletion mapping. Three minimal regions of los s were delineated; the first flanked by D13S120 and D13S219, the second by D13S126 and D13S119, and the third by D13S137 and 13qter, These 3 regions w ere linked to BRCA2 on 13q12, RBI on 13q14, and 13q14.3-ter, respectively. Seven and 4 cases showed LOH either on 13q12 or 13q14, respectively. Ninete en cases showed LOH of both loci separately. One NPC displayed 13q12 and 13 q14.3-ter LOH. RE protein expression was detectable in 76% of the cases. Te n out of 15 cases with the allelic losses limited to 13q14 showed RE protei n expression. Contrasting that, 6 out of 7 cases devoid of RE protein expre ssions showed 13q14LOH. In conclusion, 13qLOH, involving 3 tumor suppressor gene loci, appears to be a frequent genetic event occurring during NPC dev elopment. However, other tumor suppressor genes besides RBI, may be respons ible for the majority of 13q14LOH. (C) 1999 Wiley-Liss. Inc.