Crundwell M C, Chughtai S, Knowles M, Takle L, Luscombe M, Neoptolemos J P, Morton D G, Phillips S M
University Department of Surgery, Queen Elizabeth Hospital, Birmingham, UK.
Int J Cancer. 1996 Aug 22;69(4):295-300. doi: 10.1002/(SICI)1097-0215(19960822)69:4<295::AID-IJC10>3.0.CO;2-5.
Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer. The aim of this study was to further characterize these regions. We investigated 20 polymorphic regions on the 3 chromosome arms in 43 cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH on 22q implies that this locus has no significant role in prostate carcinogenesis. At DCC, although the overall incidence was low, tumours with LOH were mostly of high grade or had metastases, suggesting a role for this gene in prostate cancer progression. On chromosome 8p, 29% of cancers had deletions at the LPL locus on 8p22 and 60% had deletions within a region flanked by the markers D8S339 and ANKI on 8p 11.1-p21.1. Within this region, 2 distinct areas of allelic loss were observed, at one or both ANKI and D8S255, and in the region defined by the markers D8S259-D8S505. For the regions 8p22 and ANKI-D8S255, tumours with metastases had a greater frequency of LOH compared to non-metastasizing tumours, suggesting the presence of putative metastasis-suppressor genes in these regions.
以往研究表明,8号染色体短臂、22号染色体长臂和18号染色体(DCC)上的肿瘤抑制基因与前列腺癌有关。本研究的目的是进一步明确这些区域的特征。我们调查了43例前列腺癌和10例良性前列腺增生(BPH)患者3条染色体臂上的20个多态性区域。在8号染色体短臂上,72%的癌症存在等位基因缺失;在22号染色体长臂上,16%的癌症存在等位基因缺失;在DCC区域,24%的癌症存在等位基因缺失。对于BPH患者,8号染色体短臂上20%的病例存在等位基因缺失,DCC区域12%的病例存在等位基因缺失。22号染色体长臂上等位基因缺失发生率较低,表明该位点在前列腺癌发生过程中无显著作用。在DCC区域,虽然总体发生率较低,但存在等位基因缺失的肿瘤大多为高级别或已发生转移,提示该基因在前列腺癌进展中发挥作用。在8号染色体短臂上,29%的癌症在8p22的脂蛋白脂肪酶(LPL)位点存在缺失,60%的癌症在8p11.1-p21.1区域内位于标记D8S339和锚蛋白重复结构域1(ANKI)之间的区域存在缺失。在该区域内,观察到2个不同的等位基因缺失区域,分别位于ANKI和D8S255中的一个或两个位点,以及由标记D8S259-D8S505定义的区域。对于8p22和ANKI-D8S255区域,发生转移的肿瘤与未发生转移的肿瘤相比,等位基因缺失频率更高,提示这些区域存在潜在的转移抑制基因。