https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45052 MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.]]> Wed 26 Oct 2022 11:45:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37273 MSH3, PMS1, MLH3, EXO1, POLD1, POLD3 RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, LIG1, RPA1, RPA2, RPA3, POLD2, POLD4, MLH1, MSH2, MSH6, and PMS2) in 274 LLS patients. Detected variants were annotated and filtered using ANNOVAR and FILTUS software. Results: Thirteen variants were revealed in MLH1, MSH2, and MSH6, all genes previously linked to LS. Five additional genes (EXO1, POLD1, RFC1, RPA1, and MLH3) were found to harbor 11 variants of unknown significance in our sample cohort, two of them being frameshift variants. Conclusion: We have shown that other genes associated with the process of DNA MMR have a high probability of being associated with LLS families. These findings indicate that the spectrum of genes that should be tested when considering an entity like Lynch‐like syndrome should be expanded so that a more inclusive definition of this entity can be developed.]]> Wed 17 Nov 2021 16:28:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34524 Wed 06 Apr 2022 13:58:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52322 Wed 03 Apr 2024 15:14:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30018 Tue 20 Sep 2022 14:49:52 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24811 Thu 27 Jan 2022 15:55:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53956 Mon 22 Jan 2024 17:02:37 AEDT ]]>