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Role of POLE and POLD1 in familial cancer
- Source :
- Scientia, Genetics in Medicine, Digital.CSIC. Repositorio Institucional del CSIC, instname, Dipòsit Digital de la UB, Universidad de Barcelona
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- [Purpose]: Germline pathogenic variants in the exonuclease domain (ED) of polymerases POLE and POLD1 predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence of POLE and POLD1 variants in hereditary cancer are evaluated in this study. [Methods]: POLE and POLD1 were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics). Cosegregation and case–control studies, yeast-based functional assays, and tumor mutational analyses were performed for variant interpretation. [Results]: Twelve ED missense variants, 6 loss-of-function, and 23 outside-ED predicted-deleterious missense variants, all with population allele frequencies<br />This work was funded by the Spanish Ministry of Science and Innovation, cofunded by FEDER funds (SAF2016-80888-R, SAF2015-68016-R, Severo Ochoa SVP-2014-068895 contract [L.M.-P.]); Instituto de Salud Carlos III (PI16/00563, PI16/00588, PI14/00613, PI19/00553, CIBERONC CB16/12/00234, CIBERESP, Sara Borrell contract [P.M.]); Government of Catalonia [AGAUR 2017SGR1282, CERCA Program]; and Fundación Olga Torres. This study was facilitated by COST Action CA17118, supported by COST (European Cooperation in Science and Technology).
- Subjects :
- fenómenos genéticos::variación genética::mutación::mutación de la línea germinal [FENÓMENOS Y PROCESOS]
Proband
Polymerase proofreading–associated polyposis
Recte - Càncer - Aspectes genètics
Colorectal cancer
Genetic counseling
Population
Còlon - Càncer - Aspectes genètics
Biology
Article
Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation [PHENOMENA AND PROCESSES]
Germline
PPAP
Endometrial cancer
Càncer colorectal
Malalties hereditàries
Ultramutated phenotype
medicine
Humans
Missense mutation
Poly-ADP-Ribose Binding Proteins
education
Allele frequency
Germ-Line Mutation
Genetics (clinical)
Exonuclease domain
DNA Polymerase III
Genetics
education.field_of_study
Malalties transmissibles - Teoria germinal
POLD1
ultramutated phenotype
DNA Polymerase II
medicine.disease
polymerase proofreading–associated polyposis
Càncer d'endometri
Neoplasms::Neoplasms::Neoplastic Syndromes, Hereditary::Colorectal Neoplasms, Hereditary Nonpolyposis [DISEASES]
Hereditary colorectal cancer
Mutation
hereditary colorectal cancer
neoplasias::neoplasias::síndromes neoplásicos hereditarios::neoplasias colorrectales hereditarias sin poliposis [ENFERMEDADES]
exonuclease domain
Colorectal Neoplasms
Genetic diseases
Subjects
Details
- ISSN :
- 10983600
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Genetics in Medicine
- Accession number :
- edsair.doi.dedup.....359c40a1763da19d13d5833ef08af076