Distinct regions of allelic loss on 13q in prostate cancer.
Distinct regions of allelic loss on 13q in prostate cancer.
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发表时间：
1996-03
期刊：
影响因子：
11.2
通讯作者：
K. Cooney;Jon C. Wetzel;S. Merajver;Jill A. Macoska;T. Singleton;K. Wojno
中科院分区：
文献类型：
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作者：
K. Cooney;Jon C. Wetzel;S. Merajver;Jill A. Macoska;T. Singleton;K. Wojno
据报道，涉及13号染色体长臂的杂合性缺失（LOH）发生在多达三分之一的原发性前列腺癌中。13q上可能在前列腺癌发展中起重要作用的候选肿瘤抑制基因包括视网膜母细胞瘤易感基因（RBI）和与遗传性乳腺癌相关的基因（BRCA2）。为了确定前列腺癌中13q等位基因丢失的模式，使用横跨整个染色体臂的9个定位多态性标记进行LOH分析。根治性前列腺切除术后，40例前列腺癌患者中有19例（48%）至少有一种标记物的基因丢失。此外，40例病例中有13例（33%）有证据表明等位基因丢失涉及含有RB1的13q14区域。为了验证RB1是该区域靶向肿瘤抑制基因的假设，我们使用免疫组织化学技术对40例患者中的37例进行了pRB表达评估，pRB是RB1的蛋白产物。通过分析，37例前列腺肿瘤中有8例（22%）没有pRB表达。然而，用基因内标记评估RB1的等位基因缺失与pRB表达缺失无关（Fisher精确检验，P=0.375）。综上所述，这些数据证实了13q14共同区域的等位基因缺失发生在大约三分之一的前列腺癌中。RB1的LOH与pRB表达缺失缺乏相关性表明在该区域存在另一种在前列腺癌中重要的肿瘤抑制基因。
Loss of heterozygosity (LOH) involving the long arm of chromosome 13 has been reported to occur in as many as one third of primary prostate cancers. Candidate tumor suppressor genes on 13q that may be important in the development of prostate cancer include the retinoblastoma susceptibility gene (RBI) and a gene associated with inherited breast cancer (BRCA2). To define the pattern of allelic loss of 13q in prostate cancer, LOH analysis was performed using nine mapped polymorphic markers spanning the entire chromosomal arm. Nineteen (48%) of 40 prostate cancer cases obtained following radical prostatectomy demonstrated atllelic loss with at least one marker. Furthermore, 13 (33%) of 40 cases had evidence of allelic loss involving a region of 13q14 containing RB1. To test the hypothesis that RB1 is the targeted tumor suppressor gene in this region, 37 of 40 cases were assessed for expression of pRB, the protein product of RB1 using immunohistochemical techniques. By this analysis, 8 (22%) of 37 prostate tumors demonstrated no pRB expression. However, allelic loss at RB1, assessed with an intragenic marker, did not correlate with absent pRB expression (Fisher's exact test, P=0.375). Taken together, these data confirm that allelic loss of a common region of 13q14 occurs in approximately one third of prostate cancers. Lack of correlation of LOH at RB1 with absent pRB expression suggests the existence of another tumor suppressor gene in this region important in prostate cancer.