title: Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome.
abstract: Germline mutations of the tumor suppressor gene LKB1/STK11 are responsible for the Peutz-Jeghers syndrome (PJS), an autosomal-dominant disorder characterized by mucocutaneous pigmentation, hamartomatous polyps, and an increased risk of associated malignancies. In this study, we assessed the presence of pathogenic mutations in the LKB1/STK11 gene in 46 unrelated PJS families, and also carried genotype-phenotype correlation in regard of the development of cancer in 170 PJS patients belonging to these families. All LKB1/STK11 variants detected with single-strand conformational polymorphism were confirmed by direct sequencing, and those without LKB1/STK11 mutation were further submitted to Southern blot analysis for detection of deletions/rearrangements. Statistical analysis for genotype-phenotype correlation was performed. In 59% (27/46) of unrelated PJS cases, pathogenic mutations in the LKB1/STK11 gene, including 9 novel mutations, were identified. The new mutations were 2 splice site deletion-insertions, 2 missenses, 1 nonsense, and 4 abnormal splice sites. Genotype-phenotype analysis did not yield any significant differences between patients carrying mutations in LKB1/STK11 versus those without mutations, even with respect to primary biliary adenocarcinoma. This study presents the molecular characterization and cancer occurrence of a large cohort of PJS patients, increases the mutational spectrum of LKB1/STK11 allelic variants worldwide, and provides a new insight useful for clinical diagnosis and genetic counseling of PJS families.
authors.affiliation: Centre Médico-Chirurgical Rond-Point-Plainpalais et Département de biologie cellulaire, Unité de recherche des maladies prédisposant aux cancers gastro-intestinaux, Université de Genève, Genève, Switzerland. mehenni@cellbio.unige.ch
authors.forename: Hamid
authors.initials: H
authors.lastname: Mehenni
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Resta
authors.forename: Ginevra
authors.initials: G
authors.lastname: Guanti
authors.forename: Louisa
authors.initials: L
authors.lastname: Mota-Vieira
authors.forename: Aaron
authors.initials: A
authors.lastname: Lerner
authors.forename: Mohammed
authors.initials: M
authors.lastname: Peyman
authors.forename: Kim A
authors.initials: KA
authors.lastname: Chong
authors.forename: Larbi
authors.initials: L
authors.lastname: Aissa
authors.forename: Ali
authors.initials: A
authors.lastname: Ince
authors.forename: Angel
authors.initials: A
authors.lastname: Cosme
authors.forename: Michael C
authors.initials: MC
authors.lastname: Costanza
authors.forename: Colette
authors.initials: C
authors.lastname: Rossier
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
authors.forename: Randall W
authors.initials: RW
authors.lastname: Burt
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D005260:Female; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases