Features of Patients With Hereditary Mixed Polyposis Syndrome Caused by Duplication of GREM1 and Implications for Screening and Surveillance

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 152; no. 8; pp. 1876 - 1880.e1
• Main Authors: Lieberman, S, Walsh, T, Schechter, M, Adar, T, Goldin, E, Beeri, R, Sharon, N, Baris, H, Ben Avi, L, Half, E, Lerer, I, Shirts, B.H, Pritchard, C.C, Tomlinson, I, King, M.C, Levy-Lahad, E, Peretz, T, Goldberg, Y
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017
• Subjects: Adenomatous Polyposis Coli - diagnosis; Adenomatous Polyposis Coli - ethnology; Adenomatous Polyposis Coli - genetics; Adenomatous Polyposis Coli - pathology; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Colon - pathology; Colon Cancer Susceptibility; Colonoscopy; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis; Colorectal Neoplasms, Hereditary Nonpolyposis - ethnology; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology; CRC; Disease Progression; DNA Mutational Analysis; Early Detection of Cancer - methods; Female; Gastroenterology and Hepatology; Gene Duplication; Genetic Predisposition to Disease; Heredity; HMPS1; Humans; Intercellular Signaling Peptides and Proteins - genetics; Israel; Jews - genetics; Male; Middle Aged; Molecular Diagnostic Techniques; Mutation; Pedigree; Phenotype; Polyposis; Time Factors; Young Adult; HMPS1; colon cancer susceptibility; CRC; polyposis; APC; FAP; AJ; Colon Cancer Susceptibility; Polyposis; TVA
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2017.02.014

Abstract Hereditary mixed polyposis syndrome is a rare colon cancer predisposition syndrome caused by a duplication of a non-coding 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 extra-colonic 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.