title: Features of Patients With Hereditary Mixed Polyposis Syndrome Caused by Duplication of GREM1 and Implications for Screening and Surveillance.
abstract: Hereditary mixed polyposis syndrome is a rare colon cancer predisposition syndrome caused by a duplication of a noncoding sequence near the gremlin 1, DAN family BMP antagonist gene (GREM1) originally described in Ashkenazi Jews. Few families with GREM1 duplications have been described, so there are many questions about detection and management. We report 4 extended families with the duplication near GREM1 previously found in Ashkenazi Jews; 3 families were identified at cancer genetic clinics in Israel and 1 family was identified in a cohort of patients with familial colorectal cancer. Their clinical features include extracolonic tumors, onset of polyps in adolescence, and rapid progression of some polyps to advanced adenomas. One family met diagnostic criteria for Lynch syndrome. Expansion of the hereditary mixed polyposis syndrome phenotype can inform surveillance strategies for carriers of GREM1 duplications.
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Lieberman
authors.affiliation: Department of Medicine, Department of Genome Sciences, University of Washington, Seattle, Washington.
authors.forename: Tom
authors.initials: T
authors.lastname: Walsh
authors.affiliation: Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Schechter
authors.affiliation: Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Adar
authors.affiliation: Gastroenterology Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Goldin
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Beeri
authors.affiliation: Genetics Institute, Rambam Medical Center, Jerusalem, Israel.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Sharon
authors.affiliation: Genetics Institute, Rambam Medical Center, Jerusalem, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Baris
authors.affiliation: Department of Human Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Ben Avi
authors.affiliation: Gastroenterology Institute, Rambam Medical Center, Jerusalem, Israel.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Half
authors.affiliation: Department of Human Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Shirts
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Pritchard
authors.affiliation: Oxford Centre for Cancer Gene Research and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.affiliation: Department of Medicine, Department of Genome Sciences, University of Washington, Seattle, Washington.
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ephrat
authors.initials: E
authors.lastname: Levy-Lahad
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. Electronic address: yaelgo43@gmail.com.
authors.forename: Yael
authors.initials: Y
authors.lastname: Goldberg
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D003106:Colon / Q000473:pathology*; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins
keywords: CRC; Colon Cancer Susceptibility; HMPS1; Polyposis