Poetsch M, Dittberner T, Woenckhaus C
Institute of Forensic Medicine, Ernst Moritz Arndt-University, Kuhstrasse 30, D-17489, Greifswald, Germany.
Cancer Genet Cytogenet. 2001 Feb;125(1):21-6. doi: 10.1016/s0165-4608(00)00353-8.
A novel tumor suppressor gene, PTEN/MMAC1, on 10q23, displayed a number of mutations in solid tumors as gliomas and breast cancer. Aberrations of the long arm of chromosome 10 have been frequently detected in tumor progression of malignant melanoma of the skin by a variety of methods including cytogenetic analysis, fluorescence in situ hybridization and loss of heterozygosity analysis. Compared to previous studies, which propose an involvement of PTEN/MMAC1 in malignant melanoma mostly on the basis of data derived from cell lines and metastases, we analyzed a broader spectrum of exclusively patient derived tumor tissue by PCR and direct sequencing analysis of PTEN/MMAC1. Here, we present data of 25 primary melanomas (8 superficial spreading melanomas, 17 nodular melanomas) and 25 metastases of 41 patients. Neither loss of the complete gene nor a whole exon nor any nonsense mutations could be demonstrated. However, we detected several polymorphisms and some mutations in the introns, and in two metastatic tumors mutations with an amino acid change. Our results obtained from tissue samples underline that mutations of PTEN/MMAC1 are not an essential event in the onset of malignant melanoma of the skin, but could have an impact on tumor progression.
位于10q23的一种新型肿瘤抑制基因PTEN/MMAC1，在胶质瘤和乳腺癌等实体瘤中出现了大量突变。通过包括细胞遗传学分析、荧光原位杂交和杂合性缺失分析在内的多种方法，在皮肤恶性黑色素瘤的肿瘤进展过程中经常检测到10号染色体长臂的畸变。与之前主要基于细胞系和转移灶数据提出PTEN/MMAC1参与恶性黑色素瘤的研究相比，我们通过对PTEN/MMAC1进行PCR和直接测序分析，对更广泛的仅来源于患者的肿瘤组织进行了分析。在此，我们展示了41例患者的25例原发性黑色素瘤（8例浅表扩散性黑色素瘤，17例结节性黑色素瘤）和25例转移灶的数据。既未发现完整基因缺失、整个外显子缺失，也未发现任何无义突变。然而，我们在这些肿瘤组织中检测到了几个多态性位点以及内含子中的一些突变，并且在两个转移瘤中检测到了导致氨基酸改变的突变。我们从组织样本中获得的结果强调，PTEN/MMAC1突变并非皮肤恶性黑色素瘤发病的必要事件，但可能对肿瘤进展产生影响。
