dc.contributor.author | Palles, C | |
dc.contributor.author | West, HD | |
dc.contributor.author | Chew, E | |
dc.contributor.author | Galavotti, S | |
dc.contributor.author | Flensburg, C | |
dc.contributor.author | Grolleman, JE | |
dc.contributor.author | Jansen, EAM | |
dc.contributor.author | Curley, H | |
dc.contributor.author | Chegwidden, L | |
dc.contributor.author | Arbe-Barnes, EH | |
dc.contributor.author | Lander, N | |
dc.contributor.author | Truscott, R | |
dc.contributor.author | Pagan, J | |
dc.contributor.author | Bajel, A | |
dc.contributor.author | Sherwood, K | |
dc.contributor.author | Martin, L | |
dc.contributor.author | Thomas, H | |
dc.contributor.author | Georgiou, D | |
dc.contributor.author | Fostira, F | |
dc.contributor.author | Goldberg, Y | |
dc.contributor.author | Adams, DJ | |
dc.contributor.author | van der Biezen, SAM | |
dc.contributor.author | Christie, M | |
dc.contributor.author | Clendenning, M | |
dc.contributor.author | Thomas, LE | |
dc.contributor.author | Deltas, C | |
dc.contributor.author | Dimovski, AJ | |
dc.contributor.author | Dymerska, D | |
dc.contributor.author | Lubinski, J | |
dc.contributor.author | Mahmood, K | |
dc.contributor.author | van der Post, RS | |
dc.contributor.author | Sanders, M | |
dc.contributor.author | Weitz, J | |
dc.contributor.author | Taylor, JC | |
dc.contributor.author | Turnbull, C | |
dc.contributor.author | Vreede, L | |
dc.contributor.author | van Wezel, T | |
dc.contributor.author | Whalley, C | |
dc.contributor.author | Arnedo-Pac, C | |
dc.contributor.author | Caravagna, G | |
dc.contributor.author | Cross, W | |
dc.contributor.author | Chubb, D | |
dc.contributor.author | Frangou, A | |
dc.contributor.author | Gruber, AJ | |
dc.contributor.author | Kinnersley, B | |
dc.contributor.author | Noyvert, B | |
dc.contributor.author | Church, D | |
dc.contributor.author | Graham, T | |
dc.contributor.author | Houlston, R | |
dc.contributor.author | Lopez-Bigas, N | |
dc.contributor.author | Sottoriva, A | |
dc.contributor.author | Wedge, D | |
dc.contributor.author | Genomics England Research Consortium, | |
dc.contributor.author | CORGI Consortium, | |
dc.contributor.author | WGS500 Consortium, | |
dc.contributor.author | Jenkins, MA | |
dc.contributor.author | Kuiper, RP | |
dc.contributor.author | Roberts, AW | |
dc.contributor.author | Cheadle, JP | |
dc.contributor.author | Ligtenberg, MJL | |
dc.contributor.author | Hoogerbrugge, N | |
dc.contributor.author | Koelzer, VH | |
dc.contributor.author | Rivas, AD | |
dc.contributor.author | Winship, IM | |
dc.contributor.author | Ponte, CR | |
dc.contributor.author | Buchanan, DD | |
dc.contributor.author | Power, DG | |
dc.contributor.author | Green, A | |
dc.contributor.author | Tomlinson, IPM | |
dc.contributor.author | Sampson, JR | |
dc.contributor.author | Majewski, IJ | |
dc.contributor.author | de Voer, RM | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-07-19T10:13:31Z | |
dc.date.available | 2022-07-19T10:13:31Z | |
dc.date.issued | 2022-05-05 | |
dc.identifier | S0002-9297(22)00114-8 | |
dc.identifier.citation | American Journal of Human Genetics, 2022, 109 (5), pp. 953 - 960 | |
dc.identifier.issn | 0002-9297 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5239 | |
dc.identifier.eissn | 1537-6605 | |
dc.identifier.eissn | 1537-6605 | |
dc.identifier.doi | 10.1016/j.ajhg.2022.03.018 | |
dc.description.abstract | We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5'-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management. | |
dc.format | Print-Electronic | |
dc.format.extent | 953 - 960 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.relation.ispartof | American Journal of Human Genetics | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | 5′-methylcytosine deamination | |
dc.subject | colorectal cancer | |
dc.subject | mutational signature | |
dc.subject | mutator phenotype | |
dc.subject | polyposis | |
dc.subject | Adenomatous Polyposis Coli | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Endodeoxyribonucleases | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Germ Cells | |
dc.subject | Germ-Line Mutation | |
dc.subject | Humans | |
dc.subject | Uveal Neoplasms | |
dc.title | Germline MBD4 deficiency causes a multi-tumor predisposition syndrome. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-03-30 | |
dc.date.updated | 2022-07-19T10:13:02Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.ajhg.2022.03.018 | |
rioxxterms.licenseref.startdate | 2022-05-05 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35460607 | |
pubs.issue | 5 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.publication-status | Published | |
pubs.volume | 109 | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Evol Genomics & Modelling | |
dc.contributor.icrauthor | Turnbull, Clare | |
dc.contributor.icrauthor | Kinnersley, Benjamin | |
dc.contributor.icrauthor | Graham, Trevor | |
dc.contributor.icrauthor | Houlston, Richard | |
dc.contributor.icrauthor | Sottoriva, Andrea | |
icr.provenance | Deposited by Mr Arek Surman on 2022-07-19. Deposit type is initial. No. of files: 1. Files: Germline MBD4 deficiency causes a multi-tumor predisposition syndrome.pdf | |