Show simple item record

dc.contributor.authorEllison, Gen_US
dc.contributor.authorAhdesmäki, Men_US
dc.contributor.authorLuke, Sen_US
dc.contributor.authorWaring, PMen_US
dc.contributor.authorWallace, Aen_US
dc.contributor.authorWright, Ren_US
dc.contributor.authorRöthlisberger, Ben_US
dc.contributor.authorLudin, Ken_US
dc.contributor.authorMerkelbach-Bruse, Sen_US
dc.contributor.authorHeydt, Cen_US
dc.contributor.authorLigtenberg, MJLen_US
dc.contributor.authorMensenkamp, ARen_US
dc.contributor.authorde Castro, DGen_US
dc.contributor.authorJones, Ten_US
dc.contributor.authorVivancos, Aen_US
dc.contributor.authorKondrashova, Oen_US
dc.contributor.authorPauwels, Pen_US
dc.contributor.authorWeyn, Cen_US
dc.contributor.authorHahnen, Een_US
dc.contributor.authorHauke, Jen_US
dc.contributor.authorSoong, Ren_US
dc.contributor.authorLai, Zen_US
dc.contributor.authorDougherty, Ben_US
dc.contributor.authorCarr, THen_US
dc.contributor.authorJohnson, Jen_US
dc.contributor.authorMills, Jen_US
dc.contributor.authorBarrett, JCen_US
dc.date.accessioned2018-02-14T10:50:41Z
dc.date.issued2018-03en_US
dc.identifier.citationHuman mutation, 2018, 39 (3), pp. 394 - 405en_US
dc.identifier.issn1059-7794en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1072
dc.identifier.eissn1098-1004en_US
dc.identifier.doi10.1002/humu.23375en_US
dc.description.abstractOvarian cancer patients with germline or somatic pathogenic variants benefit from treatment with poly ADP ribose polymerase (PARP) inhibitors. Tumor BRCA1/2 testing is more challenging than germline testing as the majority of samples are formalin-fixed paraffin embedded (FFPE), the tumor genome is complex, and the allelic fraction of somatic variants can be low. We collaborated with 10 laboratories testing BRCA1/2 in tumors to compare different approaches to identify clinically important variants within FFPE tumor DNA samples. This was not a proficiency study but an inter-laboratory comparison to identify common issues. Each laboratory received the same tumor DNA samples ranging in genotype, quantity, quality, and variant allele frequency (VAF). Each laboratory performed their preferred next-generation sequencing method to report on the variants. No false positive results were reported in this small study and the majority of methods detected the low VAF variants. A number of variants were not detected due to the bioinformatics analysis, variant classification, or insufficient DNA. The use of hybridization capture or short amplicon methods are recommended based on a bioinformatic assessment of the data. The study highlights the importance of establishing standards and standardization for tBRCA testing particularly when the test results dictate clinical decisions regarding life extending therapies.en_US
dc.formatPrint-Electronicen_US
dc.format.extent394 - 405en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectNeoplasmsen_US
dc.subjectBRCA1 Proteinen_US
dc.subjectBRCA2 Proteinen_US
dc.subjectComputational Biologyen_US
dc.subjectGene Frequencyen_US
dc.subjectGenotypeen_US
dc.subjectExonsen_US
dc.subjectGenetic Testingen_US
dc.subjectDNA Copy Number Variationsen_US
dc.subjectPractice Patterns, Physicians'en_US
dc.titleAn evaluation of the challenges to developing tumor BRCA1 and BRCA2 testing methodologies for clinical practice.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-11-26en_US
rioxxterms.versionofrecord10.1002/humu.23375en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2018-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHuman mutationen_US
pubs.issue3en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume39en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorMarsden,en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record