Deichmann M, Thome M, Benner A, Egner U, Hartschuh W, Näher H
Department of Dermatology, University Clinics of Heidelberg, Vossstrasse 2, 69115 Heidelberg, Germany.
Br J Cancer. 2002 Dec 2;87(12):1431-6. doi: 10.1038/sj.bjc.6600653.
PTEN/MMAC1, a tumour suppressor gene located on chromosome 10q23.3, has been found to be deleted in several types of human malignancies. As the chromosomal region 10q22-qter commonly is affected by losses in melanomas, we addressed this gene as tumour suppressor candidate in melanomas. Investigating PTEN/MMAC1 expression at mRNA level by semi-quantitative reverse transcription-polymerase chain reaction, we did not find a statistically significant down-regulation in melanoma resection specimens in comparison to acquired melanocytic nevi from which melanomas quite often are known to arise. Upon immunohistochemistry, PTEN/MMAC1 protein expression in melanomas was not lost. Sequencing the PTEN/MMAC1 cDNAs in 26 melanoma resection specimens (21 primary melanomas, five metastases), we detected three point mutations and two nucleotide deletions which did not represent genetic polymorphisms. With respect to the predicted protein sequences, all three point mutations were silent whereas the two frame shifts at the extreme C-terminus resulted in a loss of the putative PDZ-targeting consensus sequence. As loss of this motif possibly impairs localization and function of PTEN/MMAC1 in the two corresponding primary tumours, alterations of this tumour suppressor protein may participate in some melanomas.
PTEN/MMAC1是一种位于10号染色体q23.3区域的肿瘤抑制基因，已发现在多种人类恶性肿瘤中存在缺失。由于10q22 - qter染色体区域在黑色素瘤中常受缺失影响，我们将该基因作为黑色素瘤中肿瘤抑制候选基因进行研究。通过半定量逆转录 - 聚合酶链反应在mRNA水平研究PTEN/MMAC1的表达，与已知常发生黑色素瘤的获得性黑素细胞痣相比，我们未在黑色素瘤切除标本中发现统计学上显著的下调。免疫组化显示，黑色素瘤中PTEN/MMAC1蛋白表达未缺失。对26个黑色素瘤切除标本（21个原发性黑色素瘤，5个转移灶）的PTEN/MMAC1 cDNA进行测序，我们检测到3个点突变和2个核苷酸缺失，这些并非基因多态性。就预测的蛋白质序列而言，所有3个点突变均为沉默突变，而极端C末端的2个移码导致推定的PDZ靶向共有序列缺失。由于该基序的缺失可能损害PTEN/MMAC1在两个相应原发性肿瘤中的定位和功能，这种肿瘤抑制蛋白的改变可能参与了某些黑色素瘤的发生。
