title: Double germline mutations in APC and BRCA2 in an individual with a pancreatic tumor.
abstract: We report on three brothers affected by pancreatic tumors, all due to different causes, including mutations associated with two different cancer predisposition syndromes in the same individual. In the index patient a germline mutation both in the APC and BRCA2 gene was identified while one affected brother showed the BRCA2 mutation only and another brother is supposed to have developed pancreatic cancer due to multiple non-genetic risk factors. We outline the impact of a double germline mutation in two tumor predisposition genes in one individual and proven heterogeneity of multiple cases of pancreatic tumors in one family. With the growing implementation of next generation sequence based panel testing for multiple genes involved in tumor predisposition syndromes, relevant variants in two (or more) genes will be found more frequently. This family illustrates the importance of family studies, especially when using gene panel tests.
authors.affiliation: Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. caroline.goehringer@med.uni-heidelberg.de.
authors.forename: Caroline
authors.initials: C
authors.lastname: Goehringer
authors.affiliation: Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sutter
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gebert
authors.affiliation: Department of Surgery, Philipps-University Marburg, Baldingerstraße, 35043, Marburg, Germany.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Slater
authors.affiliation: Department of Psychosomatic and General Clinical Medicine, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Keller
authors.affiliation: Department of General Surgery, Heidelberg University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Treiber
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Marchioninistraße 15, 81377, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ganschow
authors.affiliation: Faculty of Medicine and Health Sciences, University of Oldenburg, Carl-von-Ossietzky-Str. 9-11, 26129, Oldenburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kadmon
authors.affiliation: Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Moog
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000601:surgery; D000328:Adult; D000368:Aged; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics; D002760:Cholangiopancreatography, Endoscopic Retrograde; D015179:Colorectal Neoplasms / Q000235:genetics; D004379:Duodenal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D004938:Esophageal Neoplasms / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D010375:Pedigree; D016737:Proctocolectomy, Restorative
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: APC gene; BRCA2 gene; Double germline mutation; Familial adenomatous polyposis; Familial pancreatic cancer; Hereditary breast and ovarian cancer syndrome; Hereditary pancreatic cancer; Pancreatic cancer; Tumor disposition syndrome