Kiaris H, Spanakis N, Ergazaki M, Sourvinos G, Spandidos D A
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Cancer Lett. 1995 Oct 20;97(1):129-34. doi: 10.1016/0304-3835(95)03963-w.
Recent investigations revealed that the 9p arm and 17q arm of human chromosomes harbour tumour suppressor genes (TSGs) with an important role in multistage carcinogenesis. At the 9p arm is located the p16 (MTS1) TSG and probably others with an effect on various human tumours such as acute lymphoblastic leukaemia, bladder cancer, gliomas, malignant mesotheliomas, melanomas and non-small cell lung carcinomas. In addition, the 17q arm harbours BRCA1 TSG which is responsible for approximately 80% of the familial breast/ovarian cancer cases. In order to investigate the implication of these performed a loss of heterozygosity (LOH) analysis with 10 polymorphic microsatellite markers (three at the 17q arm surrounding the BRCA1 region and seven at the 9p arm). Fourteen of the 17 (82%) tumours exhibited deletions at 9p. The highest incidence of LOH (6/13, 46%) was found for the marker D9S157 at 9p22. One sample exhibited deletion of all the informative markers tested indicating deletion of the complete 9p arm. No homozygous deletions were found. LOH at the 17q arm near the BRCA1 locus was found in 6 (35%) among 17 specimens. The results of this study indicate that allelic deletions at 9p are frequent in the development of laryngeal tumours. The highest incidence of LOH was found for the marker D9S157 which is near, but distinct from the location of p16 (MTS1) tumour suppressor gene, indicating the presence of multiple tumour suppressor genes within this chromosomal region. In addition, BRCA1 TSG is implicated in the development of laryngeal tumours.
最近的研究表明，人类染色体的9号染色体短臂（9p）和17号染色体长臂（17q）含有肿瘤抑制基因（TSG），这些基因在多阶段致癌过程中发挥着重要作用。9号染色体短臂上有p16（MTS1）肿瘤抑制基因，可能还有其他对多种人类肿瘤有影响的基因，如急性淋巴细胞白血病、膀胱癌、神经胶质瘤、恶性间皮瘤、黑色素瘤和非小细胞肺癌。此外，17号染色体长臂上有BRCA1肿瘤抑制基因，约80%的家族性乳腺癌/卵巢癌病例与之相关。为了研究这些基因的作用，使用10个多态性微卫星标记进行了杂合性缺失（LOH）分析（17号染色体长臂上围绕BRCA1区域的3个，9号染色体短臂上的7个）。17个肿瘤中有14个（82%）在9p处出现缺失。在9p22的标记D9S157处发现的杂合性缺失发生率最高（6/13，46%）。一个样本显示所有检测的信息性标记均缺失，表明整个9号染色体短臂缺失。未发现纯合缺失。在17个样本中，有6个（35%）在BRCA1基因座附近的17号染色体长臂上发现杂合性缺失。本研究结果表明，9p处的等位基因缺失在喉肿瘤发生过程中很常见。在靠近但不同于p16（MTS1）肿瘤抑制基因位置的标记D9S157处发现的杂合性缺失发生率最高，表明该染色体区域内存在多个肿瘤抑制基因。此外，BRCA1肿瘤抑制基因与喉肿瘤的发生有关。
