Ueda T, Emi M, Suzuki H, Komiya A, Akakura K, Ichikawa T, Watanabe M, Shiraishi T, Masai M, Igarashi T, Ito H
Department of Urology, Chiba University School of Medicine, Japan.
Genes Chromosomes Cancer. 1999 Mar;24(3):183-90.
Frequent allelic losses on chromosome arm 13q are observed in carcinomas of the head and neck, breast, ovary, and pituitary gland. We analyzed 59 primary prostate tumors (stage B, 18 patients; C, 12 patients; D1, 4 patients; and endocrine therapy-resistant cancer death, 25 patients), as well as 18 metastatic tissues from 14 of the 25 cancer death patients for loss of heterozygosity (LOH) using 35 microsatellite markers on chromosome arm 13q. Of the 59 primary tumors, 31 (53%) showed LOH involving at least one locus. Detailed deletion mapping identified a distinct commonly deleted region in the I-cM interval flanked by D13S153 and D13S273 on 13q14 and this region overlapped a part of the RB1 gene. Paired DNAs were available from both primary and metastatic tumors in the 14 cases of cancer death; among those pairs, we detected LOH on 13q in seven (50%) primary tumors, and in all metastatic foci (P = 0.0029). Moreover, the regions lost in metastatic tissues were more extensive than those seen in the corresponding primary tumors. These results suggest that inactivation of a putative tumor suppressor gene(s) including the RB1 gene on 13q14 plays an important role in human prostate cancer.
在头颈癌、乳腺癌、卵巢癌和垂体癌中均观察到13号染色体长臂上频繁出现等位基因缺失。我们使用位于13号染色体长臂上的35个微卫星标记,分析了59例原发性前列腺肿瘤(B期18例、C期12例、D1期4例以及内分泌治疗抵抗性癌死亡患者25例),以及25例癌症死亡患者中14例患者的18个转移组织,以检测杂合性缺失(LOH)。在59例原发性肿瘤中,31例(53%)显示存在涉及至少一个位点的LOH。详细的缺失图谱分析确定了13q14上位于D13S153和D13S273侧翼的1-cM区间内一个明显的常见缺失区域,该区域与RB1基因的一部分重叠。在14例癌症死亡患者的原发性肿瘤和转移肿瘤中均获取了配对DNA;在这些配对样本中,我们在7例(50%)原发性肿瘤以及所有转移灶中检测到13q上存在LOH(P = 0.0029)。此外,转移组织中缺失的区域比相应原发性肿瘤中所见的更为广泛。这些结果表明,包括13q14上RB1基因在内的一个假定的肿瘤抑制基因失活在人类前列腺癌中起重要作用。