{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:46:19Z","timestamp":1769561179437,"version":"3.49.0"},"reference-count":16,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2001,3,15]]},"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Germline mutations of the<jats:italic>STK11\/LKB1<\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec sec-type=\"methods\">\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We report here the analysis of the <jats:italic>STK11\/LKB1<\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Germline deleterious mutation of the <jats:italic>STK11\/LKB1<\/jats:italic> 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<jats:italic>STK11\/LKB1<\/jats:italic> alteration. Analysis of clinical data indicates that the cancer associated risk is markedly different in the two groups. PJS patients with no identified<jats:italic>STK11\/LKB1<\/jats:italic> mutation are at major risk for proximal biliary adenocarcinoma, an infrequent tumour in the general population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSION<\/jats:title>\n                  <jats:p>Up to 30% of PJS patients are caused by mutation in an unidentified gene that confers high susceptibility to cancer development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.38.6.356","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:38:40Z","timestamp":1027751920000},"page":"356-360","source":"Crossref","is-referenced-by-count":72,"title":["Peutz-Jeghers families unlinked to<i>STK11\/LKB1<\/i> gene mutations are highly predisposed to primitive biliary adenocarcinoma"],"prefix":"10.1136","volume":"38","author":[{"given":"Sylviane","family":"Olschwang","sequence":"first","affiliation":[{"name":"aINSERM U434, 27 rue Juliette Dodu, 75010 Paris, France, \n\nbCEPH, Paris, France, \n\ncCHU Saint-Antoine, Service de Chirurgie Digestive, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Boisson","sequence":"additional","affiliation":[{"name":"aINSERM U434, 27 rue Juliette Dodu, 75010 Paris, France, \n\nbCEPH, Paris, France, \n\ncCHU Saint-Antoine, Service de Chirurgie Digestive, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Thomas","sequence":"additional","affiliation":[{"name":"aINSERM U434, 27 rue Juliette Dodu, 75010 Paris, France, \n\nbCEPH, Paris, France, \n\ncCHU Saint-Antoine, Service de Chirurgie Digestive, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2001,6,1]]},"reference":[{"key":"2025100521450102000_38.6.356.1","doi-asserted-by":"publisher","DOI":"10.1038\/34432"},{"key":"2025100521450102000_38.6.356.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-38"},{"key":"2025100521450102000_38.6.356.3","first-page":"5267","article-title":"Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome.","volume":"58","author":"Gruber","year":"1998","journal-title":"Cancer Res"},{"key":"2025100521450102000_38.6.356.4","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1136\/jmg.36.5.365","article-title":"Germline mutations of the LKB1 (STK11\/LKB1) gene in Peutz-Jeghers patients.","volume":"36","author":"Wang","year":"1999","journal-title":"J Med 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cancer.","volume":"58","author":"Bignell","year":"1998","journal-title":"Cancer Res"},{"key":"2025100521450102000_38.6.356.12","first-page":"2087","article-title":"Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors.","volume":"58","author":"Avizienyte","year":"1998","journal-title":"Cancer Res"},{"key":"2025100521450102000_38.6.356.13","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.1.42"},{"key":"2025100521450102000_38.6.356.14","doi-asserted-by":"publisher","DOI":"10.1086\/302159"},{"key":"2025100521450102000_38.6.356.15","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050329"},{"key":"2025100521450102000_38.6.356.16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.8.1461"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.38.6.356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:45:07Z","timestamp":1759725907000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.38.6.356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6,1]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2001,6,1]]},"published-print":{"date-parts":[[2001,6,1]]}},"alternative-id":["10.1136\/jmg.38.6.356"],"URL":"https:\/\/doi.org\/10.1136\/jmg.38.6.356","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6,1]]}}}