title: Multiple colon carcinomas in a patient with Cowden syndrome.
abstract: Cowden syndrome is a non-adenomatous gastrointestinal polyposis syndrome with inactivation of PTEN, a dual-phosphatase tumor suppressor gene. Patients with loss of wildtype PTEN expression from one allele carry an increased risk of malignant breast, thyroid and brain tumors. However, the risk of malignant transformation in gastrointestinal polyps is still unclear. In this study, we describe a kindred with Cowden syndrome and identify a heterozygous germline mutation causing truncation of the PTEN tumor suppressor. The index patient was a 56 year-old woman having multiple facial papules, acral keratosis, oral papillomatosis, multiple benign breast and thyroid tumors and gastrointestinal polyposis. Progression to invasive adenocarcinoma occured in two pre-existing hamartomatous polyps. Analysis of one of the carcinomas revealed somatic inactivation of the wildtype PTEN allele by exon-skipping. This case demonstrates that gastrointestinal hamartomas in Cowden syndrome patients can progress to invasive adenocarcinomas and should therefore be carefully monitored.
authors.affiliation: Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany. anja.bosserhoff@klinik.uni-regensburg.de
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Elke-Ingrid
authors.initials: EI
authors.lastname: Grussendorf-Conen
authors.forename: Albert
authors.initials: A
authors.lastname: Rübben
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000150:complications / Q000473:pathology; D018389:Codon, Nonsense / Q000235:genetics; D003110:Colonic Neoplasms / Q000150:complications / Q000473:pathology*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006223:Hamartoma Syndrome, Multiple / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000150:complications / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase