Brewster S F, Browne S, Brown K W
Department of Urology, Southmead Hospital, Bristol, United Kingdom.
J Urol. 1994 Apr;151(4):1073-7. doi: 10.1016/s0022-5347(17)35186-8.
We present a restriction fragment length polymorphism (RFLP) analysis of 29 benign and 30 malignant prostatic tumors, using polymorphic DNA probes to the putative tumor suppressor genes DCC (Deleted in Colorectal Carcinoma; chromosome 18q21.3), nm23-H1 (17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53 (17p13). Six of 23 evaluable cancers (26%) showed loss of heterozygosity (LOH) at DCC; 5 were advanced stage and one was clinically localized (p < 0.05). Mapping 18q deletions, another (advanced) cancer showed LOH at a locus distal to DCC (18q22), but no LOH at DCC. Three of 15 evaluable cancers (20%), all advanced, showed LOH at APC. Three of eight (38%) cancers, of which 2 were advanced, showed LOH at p53. One high grade/stage cancer of 21 (5%) showed LOH at nm23-H1 (and also at DCC). Combining data, allelic losses at either DCC, APC, or p53 genes were seen in 13% of localized cancers, but in 71% of advanced cancers (p < 0.002). Allelic loss involving nm23-H1 is rare in prostatic carcinoma. We suggest that loss of tumor suppressor genes DCC and/or an unidentified gene located distally on chromosome 18q, APC, or p53 may influence progression in prostatic carcinoma.
我们采用针对假定的肿瘤抑制基因DCC(结直肠癌缺失基因;18号染色体q21.3区域)、nm23-H1(17号染色体q21.3区域)、APC(腺瘤性息肉病基因;5号染色体q21区域)和p53(17号染色体p13区域)的多态性DNA探针,对29例良性前列腺肿瘤和30例恶性前列腺肿瘤进行了限制性片段长度多态性(RFLP)分析。在23例可评估的癌症中,有6例(26%)在DCC基因座出现杂合性缺失(LOH);其中5例为晚期,1例为临床局限性癌(p<0.05)。在定位18q缺失时,另一例(晚期)癌症在DCC基因座远端的一个位点(18q22)出现LOH,但在DCC基因座未出现LOH。在15例可评估的癌症中,有3例(20%)均为晚期,在APC基因座出现LOH。在8例癌症中有3例(38%),其中2例为晚期,在p53基因座出现LOH。在21例高分级/高分期癌症中有1例(5%)在nm23-H1基因座出现LOH(同时也在DCC基因座出现LOH)。综合数据来看,在局限性癌症中,13%出现了DCC、APC或p53基因的等位基因缺失,但在晚期癌症中这一比例为71%(p<0.002)。涉及nm23-H1的等位基因缺失在前列腺癌中较为罕见。我们认为,肿瘤抑制基因DCC和/或位于18号染色体q远端的一个未明确的基因、APC或p53的缺失可能会影响前列腺癌的进展。