https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51421 Wed 28 Feb 2024 15:25:16 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31996 Wed 22 Mar 2023 16:06:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37510 Wed 19 Jan 2022 15:15:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34201 In vivo genetic cell lineage tracing showed that secretory cells not only self-renew, but also give rise to ciliated cells. Analysis of a Wnt reporter mouse model and various Wnt target genes showed that the Wnt signaling pathway is involved in oviductal epithelial homoeostasis. By developing two triple-transgenic mouse models, we showed that Wnt/ ß-catenin signaling is essential for self-renewal as well as the differentiation of secretory cells. In summary, our results provide mechanistic insight into oviductal epithelial homoeostasis.]]> Wed 19 Jan 2022 15:14:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51044 Wed 16 Aug 2023 11:19:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35727 Wed 14 Jun 2023 12:38:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22608 Wed 11 Apr 2018 15:49:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27601 Wed 11 Apr 2018 15:11:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4382 G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression. Results: A comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59–3.11). Conclusion: Our data suggest that the PHB 3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations.]]> Wed 11 Apr 2018 14:48:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22556 Wed 11 Apr 2018 14:15:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19520 Wed 11 Apr 2018 09:43:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15140 Wed 11 Apr 2018 09:39:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29580 BRCA1/2 mutations have a genetic predisposition for developing OC, but not all of these women develop the disease. Epidemiological findings show that lifestyle factors such as contraceptive use and pregnancy, a progesterone dominant state, decrease the risk of getting OC. How ovarian hormones modify the risk of OC is currently unclear. Our study identifies activated Wnt signalling to be a marker for precursor lesions of OC and successfully develops a mouse model that mimics the earliest events in pathogenesis of OC by constitutively activating ßcatenin. Using this model and human OC cells, we show that oestrogen promotes and progesterone suppresses the growth of OC cells.]]> Wed 09 Feb 2022 15:54:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35526 Wed 08 Jul 2020 09:57:42 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51462 Wed 06 Mar 2024 14:35:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52889 Tue 31 Oct 2023 15:47:10 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36310 Tue 22 Jun 2021 12:13:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48290 Tue 14 Mar 2023 11:54:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50033 T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.]]> Thu 29 Jun 2023 13:56:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:575 Thu 25 Jul 2013 09:10:29 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30577 Thu 24 Mar 2022 11:32:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:2869 Sat 24 Mar 2018 10:42:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7711 Sat 24 Mar 2018 08:41:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9541 Sat 24 Mar 2018 08:35:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7119 Sat 24 Mar 2018 08:34:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1507 Sat 24 Mar 2018 08:30:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1729 Sat 24 Mar 2018 08:27:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10397 Sat 24 Mar 2018 08:08:45 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20955 Sat 24 Mar 2018 08:06:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18989 Sat 24 Mar 2018 08:05:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21178 BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR. Results: The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10–11.07), p = 0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated. Conclusions: This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.]]> Sat 24 Mar 2018 07:58:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20682 Sat 24 Mar 2018 07:55:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21290 BRCA1 gene increases the risk of the person developing breast and/or ovarian cancer. The prevalence and spectrum of large genomic rearrangements (LGRs) varies considerably among different tested populations. In our previous study we described three LGRs in BRCA1 (exons 13-19, exon 17 and exon 22) in Polish families at high risk of breast and ovarian cancer. In this study we analyzed a group of 550 unselected women with ovarian cancer for the three previously identified LGRs. We used a rapid, single-step and closed-tube method: high-resolution melting analysis (HRMA). In this group of unrelated patients diagnosed with ovarian cancer we found three cases with the same deletions of exon 22. This is the first recurrent large deletion in BRCA1 found in Poland. We conclude that screening for the exon 22 deletion in BRCA1 should be included in the Polish BRCA1 genetic testing panel and possibly extended into other Slavic populations.]]> Sat 24 Mar 2018 07:54:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24061 Sat 24 Mar 2018 07:09:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34256 Mon 25 Feb 2019 11:25:06 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32907 Mon 23 Sep 2019 13:50:52 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44175 Mon 10 Oct 2022 10:13:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32152 Mon 07 May 2018 14:16:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32153 Mon 07 May 2018 14:14:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35870 Fri 21 Oct 2022 11:25:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35459 Fri 16 Aug 2019 14:29:49 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47283 Fri 13 Jan 2023 10:24:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44103 Fri 07 Oct 2022 13:51:30 AEDT ]]>