Böni R, Vortmeyer A O, Burg G, Hofbauer G, Zhuang Z
Department of Dermatology, University Hospital, Zurich, Switzerland.
Melanoma Res. 1998 Aug;8(4):300-2. doi: 10.1097/00008390-199808000-00002.
A candidate tumour suppressor gene, PTEN, has recently been identified within chromosome 10q23, the locus of the Cowden syndrome/Lhermitte Duclos disease susceptibility gene. Cowden disease is an autosomal dominant cancer predisposition syndrome associated with tumours of the breast, thyroid and, less frequently, malignant melanoma. Based on the identification of mutations in sporadic breast, brain and prostate tumours, we decided to examine the potential role of PTEN in sporadic malignant melanoma. Frozen tissue from primary cutaneous melanomas (n = 23) and metastases (n = 17) were microdissected, and microsatellite markers D10S541 and D10S547, flanking the gene on both sides, were used to search for loss of heterozygosity (LOH) in the PTEN gene locus. To identify mutations within the putative tumour suppressor gene, we performed single strand conformation polymorphism (SSCP) analysis using intronic primers to amplify exons 5, 6, 7 and 8 of the PTEN gene. No LOH was detected using the polymorphic markers D10S541 and D10S547. SSCP analysis revealed no aberrant bands in the tumour specimen. Our results suggest that the PTEN gene does not play a major role in the initiation and progression of melanoma.
一个候选肿瘤抑制基因PTEN最近在10q23染色体上被发现，该区域是考登综合征/勒米特-迪克洛病易感基因的位点。考登病是一种常染色体显性遗传的癌症易感综合征，与乳腺、甲状腺肿瘤相关，较少与恶性黑色素瘤相关。基于在散发性乳腺、脑和前列腺肿瘤中发现的突变，我们决定研究PTEN在散发性恶性黑色素瘤中的潜在作用。对来自原发性皮肤黑色素瘤（n = 23）和转移灶（n = 17）的冷冻组织进行显微切割，使用位于该基因两侧的微卫星标记D10S541和D10S547来检测PTEN基因位点的杂合性缺失（LOH）。为了鉴定假定的肿瘤抑制基因内的突变，我们使用内含子引物进行单链构象多态性（SSCP）分析，以扩增PTEN基因的外显子5、6、7和8。使用多态性标记D10S541和D10S547未检测到LOH。SSCP分析在肿瘤标本中未发现异常条带。我们的结果表明，PTEN基因在黑色素瘤的发生和发展中不发挥主要作用。
