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dc.contributor.authorJanssen, Borisen
dc.contributor.authorBellis, Sarahen
dc.contributor.authorKoller, Thomasen
dc.contributor.authorTischkowitz, Marcen
dc.contributor.authorLiau, Siong-Sengen
dc.date.accessioned2019-09-30T14:09:36Z
dc.date.available2019-09-30T14:09:36Z
dc.date.issued2020-01en
dc.identifier.issn1434-5161
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/297283
dc.description.abstractPartner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous DNA recombination. Germline loss-of-function variants in the PALB2 gene may confer an increased lifetime risk of breast, pancreatic, ovarian and other cancers. However, the complete spectrum of predicted pathogenic PALB2 variants associated with each tissue type of cancer remains unknown. A systematic review is performed with the aim of cataloguing predicted pathogenic PALB2 variants in breast, ovary and pancreas cancers. All catalogued predicted pathogenic variants are analysed to assess for overlap and mutational ‘hotspots’ within gene exons. Our results showed that 911 (92.5%) cases were described in breast cancer patients, 49 (5.0%) cases were described in ovarian cancer patients, and 24 (2.4%) cases were described in pancreatic cancer patients. The top five most frequently reported predicted pathogenic PALB2 variants were c.509_510delGA, c.3113G>A, c.1592delT, c.172_175delTTGT, and c.1240C>T, accounting for 57.3% of all cases. Breast and pancreatic cancers share 5 variants whilst breast and ovarian cancers share 12 variants. Breast, ovarian and pancreatic cancers share 8 common variants. Exons with the highest mutation rates were exons 2 (6.7%), 1 (6.3%), and 3 (5.8%). This systematic review provides a quantitative catalogue of predicted pathogenic PALB2 variants described in cancers. This comprehensive analysis of the PALB2 mutational spectrum represents a useful resource for clinicians overseeing PALB2-related cancer surveillance and provides a valuable resource for future PALB2 specific research.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature
dc.subjectHumansen
dc.subjectBreast Neoplasmsen
dc.subjectPancreatic Neoplasmsen
dc.subjectOvarian Neoplasmsen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectBRCA1 Proteinen
dc.subjectBRCA2 Proteinen
dc.subjectGerm-Line Mutationen
dc.subjectExonsen
dc.subjectFemaleen
dc.subjectFanconi Anemia Complementation Group N Proteinen
dc.subjectCarcinoma, Ovarian Epithelialen
dc.titleA systematic review of predicted pathogenic PALB2 variants: an analysis of mutational overlap between epithelial cancers.en
dc.typeArticle
prism.endingPage205
prism.issueIdentifier2en
prism.publicationDate2020en
prism.publicationNameJournal of human geneticsen
prism.startingPage199
prism.volume65en
dc.identifier.doi10.17863/CAM.44332
dcterms.dateAccepted2019-09-30en
rioxxterms.versionofrecord10.1038/s10038-019-0680-7en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-01en
dc.contributor.orcidKoller, Thomas [0000-0002-8150-0677]
dc.contributor.orcidTischkowitz, Marc [0000-0002-7880-0628]
dc.identifier.eissn1435-232X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G1002543)
cam.orpheus.successThu Jan 30 10:37:53 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-04-16


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