Scala S, Bruni P, Lo Muzio L, Mignogna M, Viglietto G, Fusco A
Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, via M. Semmola, 80131 Napoli, Italy.
Int J Oncol. 1998 Oct;13(4):665-8. doi: 10.3892/ijo.13.4.665.
Cowden disease (CD) is an autosomal dominant multiple hamartoma syndrome with an elevated risk of thyroid and breast cancers. The CD susceptibility gene has recently been identified as the PTEN/MMAC1/TEP1 gene localized at 10q23 and coding for a dual specificity protein phosphatase. We report the mutational analysis of the PTEN gene in one Italian CD kindred. By using the single strand conformation polymorphism technique and subsequent direct DNA sequencing of the polymerase chain reaction product, we identified a novel mutation in the exon 5 of the PTEN gene. A heterozygous germline TGT-TAT transition was detected at the nucleotide 407; this causes the amino acid substitution cys136-tyr136 and the generation of a new NSI I restriction site. This mutation was not detected in the unaffected member of the family thereby indicating that it is causally linked to the disease. We ruled out that this mutation is a polymorphic variant because it was not detected in over 100 chromosomes analyzed. Using reverse trancriptase-polymerase chain reaction, we detected the expression of the mutant allele in lymphocytes and pathological tissues from an affected member of the family.
考登病（CD）是一种常染色体显性遗传的多发性错构瘤综合征，患甲状腺癌和乳腺癌的风险较高。最近已确定CD易感基因是位于10q23的PTEN/MMAC1/TEP1基因，该基因编码一种双特异性蛋白磷酸酶。我们报告了对一个意大利CD家系中PTEN基因的突变分析。通过使用单链构象多态性技术以及随后对聚合酶链反应产物进行直接DNA测序，我们在PTEN基因的外显子5中鉴定出一个新的突变。在核苷酸407处检测到杂合种系TGT - TAT转换；这导致氨基酸取代cys136 - tyr136，并产生一个新的NSI I限制性位点。在该家族未患病成员中未检测到这种突变，从而表明它与该疾病存在因果关系。我们排除了这种突变是多态性变体的可能性，因为在分析的100多条染色体中均未检测到它。使用逆转录 - 聚合酶链反应，我们在该家族一名患病成员的淋巴细胞和病理组织中检测到了突变等位基因的表达。
