Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma
Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma
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DOI：
10.1136/jmg.38.6.356
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发表时间：
2001-06-01
影响因子：
4
通讯作者：
Thomas, G
中科院分区：
文献类型：
--
作者：
Olschwang, S;Boisson, C;Thomas, G
STK 11/LKB 1肿瘤抑制基因（19p13.3）的种系突变是Peutz-Jeghers综合征（PJS）的原因，这是一种罕见的遗传性疾病，主要是遗传性的。除了典型的错构瘤性胃肠道息肉和口周色素性病变外，PJS还与各种部位的肿瘤发展有关。尚未对基因携带者进行具体的随访评估。此外，遗传异质性已被报道，这使得遗传consulting.Methods -我们在这里报告的STK 11/LKB 1位点的分析在一系列的34 PJS家庭，结合搜索的突变和重排的编码序列，等位基因特异性表达测试，和连锁studies.Results -生殖系有害突变的STK 11/LKB 1基因被确定在70%的情况下。第二个PJS基因座的假设得到加强，PJS家族可以分为两组的基础上，存在或不存在一个确定的STK 11/LKB 1改变。临床数据分析表明，两组的癌症相关风险存在显著差异。PJS患者没有确定的STK 11/LKB 1突变是近端胆管腺癌，一种罕见的肿瘤在一般population.Conclusion -高达30%的PJS患者的主要风险是由一个未知的基因突变，赋予癌症发展的高敏感性。
Introduction - Germline mutations of the STK11/LKB1 tumour suppressor gene (19p13.3) are responsible for Peutz-Jeghers syndrome (PJS), a rare genetic disorder, which is dominantly inherited. In addition to the typical hamartomatous gastrointestinal polyps and perioral pigmented lesions, PJS is also associated with the development of tumours in various sites. No specific follow up has yet been evaluated for gene carriers. Furthermore, genetic heterogeneity has been reported, which makes genetic counselling difficult.Methods - We report here the analysis of the STK11/LKB1 locus in a series of 34 PJS families, combining the search for mutations and rearrangements in the coding sequence, allele specific expression tests, and Linkage studies.Results - Germline deleterious mutation of the STK11/LKB1 gene were identified in 70% of cases. The hypothesis of a second PJS locus was reinforced and PJS families could be divided into two groups on the basis of the presence or absence of an identified STK11/LKB1 alteration. Analysis of clinical data indicates that the cancer associated risk is markedly different in the two groups. PJS patients with no identified STK11/LKB1 mutation are at major risk for proximal biliary adenocarcinoma, an infrequent tumour in the general population.Conclusion - Up to 30% of PJS patients are caused by mutation in an unidentified gene that confers high susceptibility to cancer development.