Latini J M, Rieger-Christ K M, Wang D S, Silverman M L, Libertino J A, Summerhayes I C
Department of Urology, Lahey Clinic, Burlington, Massachusetts, USA.
J Urol. 2001 Nov;166(5):1931-6.
We investigated the incidence of loss of heterozygosity (LOH) and microsatellite instability in sporadic prostate cancer and surrounding tissue at loci encompassing the HPC1 and PTEN genes.
Surgical specimens from 63 patients with sporadic stage T3 or T4 prostatic adenocarcinoma were analyzed for LOH and microsatellite instability. Microdissected tissue included morphologically normal foci, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma. LOH analysis was performed using 4 microsatellite markers that map in the region of the 1q24 to 25 locus of the putative prostate cancer susceptibility gene HPC1 and 4 that map in the region of the 10q23 locus of the PTEN gene.
The incidence of LOH on 10q was consistent with that previously reported in prostatic tumors. LOH associated with the PTEN locus was recorded in morphologically normal foci, BPH and adenocarcinoma. Sequence analysis of PTEN in a limited number of lesions revealed mutations in nontumor and tumor tissue. Analysis of the DS10215 locus showed significant LOH in tumor but not in benign tissue, suggestive of a tumor suppressor gene in this region associated with prostatic neoplastic progression. In contrast, no significant LOH was observed in the same tissues at 4 loci on chromosome 1q. In this study we recorded elevated levels of microsatellite instability in benign prostatic tissue with an additional increase associated with prostatic adenocarcinoma.
The low incidence of LOH in the region of the HPC1 locus in all prostate lesions studied suggests that this putative hereditary prostate cancer susceptibility locus does not appear to have a role in sporadic prostate cancer, at least not in the context of LOH. In contrast, analysis of the same tissues for LOH at chromosome 10q confirmed frequent alterations in this region linked to late stage prostate cancer. PTEN mutations in microdissected morphologically normal and BPH tissue showed alterations in nontumor tissue surrounding adenocarcinoma. Microsatellite instability was increased in adenocarcinomas over an elevated background recorded in surrounding tissues.
我们研究了散发性前列腺癌及周围组织中，包含HPC1和PTEN基因位点的杂合性缺失（LOH）发生率和微卫星不稳定性。
对63例散发性T3或T4期前列腺腺癌患者的手术标本进行LOH和微卫星不稳定性分析。显微切割组织包括形态学上正常的病灶、良性前列腺增生（BPH）和前列腺腺癌。使用4个微卫星标记进行LOH分析，这些标记位于假定的前列腺癌易感基因HPC1的1q24至25位点区域，以及4个位于PTEN基因10q23位点区域的标记。
10q上的LOH发生率与先前报道的前列腺肿瘤发生率一致。与PTEN位点相关的LOH在形态学上正常的病灶、BPH和腺癌中均有记录。对有限数量病变中的PTEN进行序列分析，发现非肿瘤组织和肿瘤组织中均有突变。对DS10215位点的分析显示，肿瘤组织中有显著的LOH，而良性组织中无，提示该区域存在与前列腺肿瘤进展相关的确肿瘤抑制基因。相比之下，在1号染色体q臂上的4个位点的相同组织中未观察到显著的LOH。在本研究中，我们记录到良性前列腺组织中微卫星不稳定性水平升高，前列腺腺癌中则进一步升高。
在所研究的所有前列腺病变中，HPC1位点区域的LOH发生率较低，这表明这个假定的遗传性前列腺癌易感位点似乎在散发性前列腺癌中不起作用，至少在LOH方面是这样。相比之下，对相同组织进行10号染色体q臂的LOH分析证实，该区域的频繁改变与晚期前列腺癌有关。显微切割的形态学上正常和BPH组织中的PTEN突变显示，腺癌周围的非肿瘤组织也有改变。腺癌中的微卫星不稳定性在周围组织升高的背景上进一步增加。
