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dc.contributor.authorTalseth-Palmer, Bente
dc.contributor.authorBauer, Denis
dc.contributor.authorSjursen, Wenche
dc.contributor.authorEvans, Tiffany-Jane
dc.contributor.authorMcPhillips, Mary
dc.contributor.authorProietto, Anthony
dc.contributor.authorOtten, Geoffrey
dc.contributor.authorSpigelman, Allan D.
dc.contributor.authorScott, Rodney J.
dc.identifier.citationCancer Medicine. 2016, 5 (5), 929-941.en_US
dc.description.abstractCausative germline mutations in mismatch repair (MMR ) genes can only be identified in ~50% of families with a clinical diagnosis of the inherited colorectal cancer (CRC ) syndrome hereditary nonpolyposis colorectal cancer (HNPCC )/Lynch syndrome (LS ). Identification of these patients are critical as they are at substantially increased risk of developing multiple primary tumors, mainly colorectal and endometrial cancer (EC ), occurring at a young age. This demonstrates the need to develop new and/or more thorough mutation detection approaches. Next‐generation sequencing (NGS ) was used to screen 22 genes involved in the DNA MMR pathway in constitutional DNA from 14 HNPCC and 12 sporadic EC patients, plus 2 positive controls. Several softwares were used for analysis and functional annotation. We identified 5 exonic indel variants, 42 exonic nonsynonymous single‐nucleotide variants (SNV s) and 1 intronic variant of significance. Three of these variants were class 5 (pathogenic) or class 4 (likely pathogenic), 5 were class 3 (uncertain clinical relevance) and 40 were classified as variants of unknown clinical significance. In conclusion, we have identified two LS families from the sporadic EC patients, one without a family history of cancer, supporting the notion for universal MMR screening of EC patients. In addition, we have detected three novel class 3 variants in EC cases. We have, in addition discovered a polygenic interaction which is the most likely cause of cancer development in a HNPCC patient that could explain previous inconsistent results reported on an intronic EXO 1 variant.en_US
dc.publisherJohn Wiley & Sons Ltden_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleTargeted next-generation sequencing of 22 mismatch repair genes identifies Lynch syndrome familiesen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalCancer Medicineen_US
dc.description.localcodeThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal