title: Duodenal cancer in a patient with Peutz-Jeghers syndrome: molecular analysis.
abstract: We experienced an unusual case of duodenal adenocarcinoma associated with Peutz-Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on the presence of mucocutaneous pigmentation of the lip and fingertips, and colonic hamartomatous polyps. Abdominal computed tomography revealed a tumor in the third portion of the duodenum extending into the pancreas head. As the tumor was pathologically determined to be adenocarcinoma at the time of surgery, pylorus-preserving pancreaticoduodenectomy was performed. We carried out molecular analyses of this patient to examine the pathway of carcinogenesis in PJS. The tumor did not show somatic mutation of the APC and K-ras genes, which is a critical step for the adenoma-carcinoma sequence in colon cancer. Importantly, a germline mutation of the STK11 gene was detected at codon 281 delC in exon 6. Moreover, the tumor showed loss of heterozygosity of the 19p marker near STK11 and somatic mutation of the p53 gene. These findings suggest that STK11 is a tumor suppressor gene regulating the development of hamartomas, and that somatic mutation of p53 subsequently promotes gastrointestinal cancer at a later stage in PJS.
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakamura
authors.forename: Shohachi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yokoi
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kashiwabara
authors.forename: Keiji
authors.initials: K
authors.lastname: Maruyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Baba
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D004379:Duodenal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases