title: Vessels' morphology in SMAD4 and BMPR1A-related juvenile polyposis.
abstract: Juvenile polyposis syndrome is a hamartomatous intestinal polyposis associated with malignant changes in 20% of patients at an early age. Germline mutations mostly involve two genes, SMAD4 and BMPR1, with no strong evidence of phenotype-genotype correlation, which could be predictive of the specific long-term evolution. In contrast, PTEN mutations are more commonly associated with Cowden and related diseases. Forty-two unrelated patients affected by juvenile polyposis syndrome were analyzed for germline alterations in the BMPR1A and SMAD4 genes, and for clinical and histological features. Deleterious mutations were found in 14/42 (33%) patients: 5 in BMPR1A and 9 in SMAD4. Low-grade adenomas were present in both SMAD4 and BMPR1A mutation carriers; only patients with SMAD4 mutations harbored carcinoma lesions (5/9). Malformative vessels were present in all SMAD4 related polyps when the mutation involved codons prior to position 423. No gastric polyps were observed in BMPR1A mutation carriers. SMAD4 germline mutations are responsible for a more aggressive digestive phenotype in patients with juvenile polyposis. The presence of malformative vessels within the stromal component might be a useful tool to drive the subsequent genetic and clinical management.
authors.affiliation: Hôpital Jean Verdier, Department of Pathology, Paris, France.
authors.forename: Adriana
authors.initials: A
authors.lastname: Handra-Luca
authors.forename: Christel
authors.initials: C
authors.lastname: Condroyer
authors.forename: Céline
authors.initials: C
authors.lastname: de Moncuit
authors.forename: Maryline
authors.initials: M
authors.lastname: Tepper
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001808:Blood Vessels / Q000473:pathology*; D052005:Bone Morphogenetic Protein Receptors, Type I; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D041981:Gastrointestinal Tract / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D011127:Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000032:analysis / Q000235:genetics*; D051901:Smad4 Protein; D013577:Syndrome; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D017978:Receptors, Growth Factor; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D017346:Protein Serine-Threonine Kinases; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I