title: Detection of a Tumor Suppressor Gene Variant Predisposing to Colorectal Cancer in an 18th Century Hungarian Mummy.
abstract: Mutations of the Adenomatous polyposis coli (APC) gene are common and strongly associated with the development of colorectal adenomas and carcinomas. While extensively studied in modern populations, reports on visceral tumors in ancient populations are scarce. To the best of our knowledge, genetic characterization of mutations associated with colorectal cancer in ancient specimens has not yet been described. In this study we have sequenced hotspots for mutations in the APC gene isolated from 18th century naturally preserved human Hungarian mummies. While wild type APC sequences were found in two mummies, we discovered the E1317Q missense mutation, known to be a colorectal cancer predisposing mutation, in a large intestine tissue of an 18th century mummy. Our data suggests that this genetic predisposition to cancer already existed in the pre-industrialization era. This study calls for similar investigations of ancient specimens from different periods and geographical locations to be conducted and shared for the purpose of obtaining a larger scale analysis that will shed light on past cancer epidemiology and on cancer evolution.
authors: Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Michal
authors: M
authors: Feldman
authors: Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Israel
authors: I
authors: Hershkovitz
authors: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Ella H
authors: EH
authors: Sklan
authors: Koret School of Veterinary Medicine, The Robert H. Smith faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors: Gila
authors: G
authors: Kahila Bar-Gal
authors: Department of Anthropology, Hungarian Natural History Museum, Budapest, Hungary.
authors: Ildikó
authors: I
authors: Pap
authors: Department of Anthropology, Hungarian Natural History Museum, Budapest, Hungary.
authors: Ildikó
authors: I
authors: Szikossy
authors: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Rina
authors: R
authors: Rosin-Arbesfeld
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000266:history*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D019943:Amino Acid Substitution; D018389:Codon, Nonsense; D003106:Colon / Q000737:chemistry; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics / Q000302:isolation & purification; D017491:Genes, APC; D049671:History, 18th Century; D006720:Homozygote; D006801:Humans; D006814:Hungary; D009106:Mummies; D017354:Point Mutation
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D018389:Codon, Nonsense; D004272:DNA, Mitochondrial; D004247:DNA