Exome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway

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dc.contributor.authorVan der Merwe, Nicoleen_ZA
dc.contributor.authorPeeters, Armand V.en_ZA
dc.contributor.authorPienaar, Fredrieka M.en_ZA
dc.contributor.authorBezuidenhout, Juanitaen_ZA
dc.contributor.authorVan Rensburg, Susan J.en_ZA
dc.contributor.authorKotze, Maritha J.en_ZA
dc.date.accessioned2018-01-23T12:07:49Z
dc.date.available2018-01-23T12:07:49Z
dc.date.issued2017-02-22
dc.descriptionCITATION: Van Der Merwe, N., et al. 2017. Exome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway. International Journal of Molecular Sciences, 18(2):467, doi:10.3390/ijms18020467.
dc.descriptionThe original publication is available at http://www.mdpi.com
dc.description.abstractENGLISH ABSTRACT: Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two BRCA1/2 mutation-negative breast cancer patients from the same family for WES. Homozygosity for the MTHFR 677 C>T mutation detected during this PSGT pre-screen step was considered insufficient to cause bilateral breast cancer in the index case and her daughter diagnosed with early-onset breast cancer (<30 years). Extended genetic testing using WES identified the RAD50 R385C missense mutation in both cases. This rare variant with a minor allele frequency (MAF) of <0.001 was classified as a VUS after exclusion in an affected cousin and extended genotyping in 164 unrelated breast cancer patients and 160 controls. Detection of functional polymorphisms (MAF > 5%) in the folate pathway in all three affected family members is consistent with inheritance of the luminal-type breast cancer in the family. PSGT assisted with the decision to pursue extended genetic testing and facilitated clinical interpretation of WES aimed at reduction of recurrence risk.en_ZA
dc.description.urihttp://www.mdpi.com/1422-0067/18/2/467
dc.description.versionPublisher's version
dc.format.extent17 pages
dc.identifier.citationVan Der Merwe, N., et al. 2017. Exome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway. International Journal of Molecular Sciences, 18(2):467, doi:10.3390/ijms18020467
dc.identifier.issn1422-0067 (online)
dc.identifier.issn1661-6596 (print)
dc.identifier.otherdoi:10.3390/ijms18020467
dc.identifier.urihttp://hdl.handle.net/10019.1/103083
dc.language.isoen_ZAen_ZA
dc.publisherMDPI
dc.rights.holderAuthors retain copyright
dc.subjectBreast -- Canceren_ZA
dc.subjectBreast cancer genesen_ZA
dc.subjectPharmacogenomicsen_ZA
dc.subjectPathologyen_ZA
dc.subjectBreast -- Cancer -- Diagnosisen_ZA
dc.titleExome sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathwayen_ZA
dc.typeArticleen_ZA
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