scholarly journals Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene

Oncotarget ◽  
2017 ◽  
Vol 8 (31) ◽  
pp. 50930-50940 ◽  
Author(s):  
Ed Dicks ◽  
Honglin Song ◽  
Susan J. Ramus ◽  
Elke Van Oudenhove ◽  
Jonathan P. Tyrer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Large Scale ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Whole Exome ◽  
Cancer Susceptibility Gene

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

scholarly journals Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer

2020 ◽  
pp. jmedgenet-2019-106739 ◽  
Author(s):  
Honglin Song ◽  
Ed M Dicks ◽  
Jonathan Tyrer ◽  
Maria Intermaggio ◽  
Georgia Chenevix-Trench ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Candidate Genes ◽  
Susceptibility Gene ◽  
Susceptibility Genes ◽  
European Ancestry ◽  
Ovarian Cancer Risk ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Deleterious Mutations ◽  
Increased Risk

PurposeThe known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.MethodsWe sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics.ResultsThe ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive.ConclusionsWe have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.

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