Background Pathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases. We aim to evaluate the disease spectrum of breast cancer susceptibility genes (BCSGs) to develop a comprehensive resource of gene-disease associations for clinicians. Methods Thirteen genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, RECQL, STK11, and TP53), that have been conclusively established as BCSGs by the Clinical Genome Resource (ClinGen) and the NCCN guidelines, were investigated. For these thirteen genes, potential gene-disease associations were identified and evaluated based on six genetic resources (ClinGen, NCCN, OMIM, Genetics Home Reference, GeneCards and Gene-NCBI) and an additional literature review using a semiautomated natural language processing (NLP) abstract classification procedure. Results A total of 40 diseases were confirmed as being associated with one or more of the 13 BCSGs by our evaluation. Malignant diseases including prostate cancer, pancreatic cancer, colorectal cancer, brain tumor, gastric cancer, ovarian cancer, and sarcoma were associated with at least 3 BCSGs. Furthermore, a total of 87 gene-disease associations were confirmed by our evaluation, of which 85% (74/87) were confirmed by ClinGen and/or NCCN. Conversely, 9 gene-disease associations absent from both ClinGen and NCCN were confirmed in the other four genetic resources (≥3) and 4 gene-disease associations were confirmed by the NLP-based procedure. Conclusion This is the first study to systematically investigate the reported disease spectrum of BCSGs in multiple sources. Our innovative approach provides a general guide for evaluating gene-disease associations and improves the clinical management for at-risk individuals.

BackgroundPathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases, which clinicians must manage for their patients. We evaluated the disease spectrum of breast cancer susceptibility genes (BCSGs) with the aim of developing a comprehensive resource of gene-disease associations for clinicians.MethodsTwelve genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RECQL, STK11, and TP53), all of which have been conclusively established as BCSGs by the Clinical Genome Resource (ClinGen) and/or the NCCN guidelines, were investigated. The potential gene-disease associations for these 12 genes were verified and evaluated based on six genetic resources (ClinGen, NCCN, OMIM, Genetics Home Reference, GeneCards, and Gene-NCBI) and an additional literature review using a semiautomated natural language processing (NLP) abstract classification procedure.ResultsForty-two diseases were found to be associated with one or more of the 12 BCSGs for a total of 86 gene-disease associations, of which 90% (78/86) were verified by ClinGen and/or NCCN. Four gene-disease associations could not be verified by either ClinGen or NCCN but were verified by at least three of the other four genetic resources. Four gene-disease associations were verified by the NLP procedure alone.ConclusionThis study is unique in that it systematically investigates the reported disease spectrum of BCSGs by surveying multiple genetic resources and the literature with the aim of developing a single consolidated, comprehensive resource for clinicians. This innovative approach provides a general guide for evaluating gene-disease associations for BCSGs, potentially improving the clinical management of at-risk individuals.

Background: Pathogenic variants in germline cancer susceptibility genes can increase the risk of a large number of diseases. Our study aims to assess the disease spectrum of gastric cancer susceptibility genes and to develop a comprehensive resource of genedisease associations for clinicians.Methods: Twenty-seven potential germline gastric cancer susceptibility genes were identified from three review articles and from six commonly used genetic information resources. The diseases associated with each gene were evaluated via a semi-structured review of six genetic resources and an additional literature review using a natural language processing (NLP)-based procedure.Results: Out of 27 candidate genes, 13 were identified as gastric cancer susceptibility genes (APC,

Loss of tooth structure in the esthetic region is a big challenge for restorative dentist as it not only involves the establishment of tooth structure but also complies microesthetics. If the tooth structure is lost near the gingival margin, then the periodontal aspect cannot be overlooked. Surgical crown lengthening and orthodontic extrusion of the remaining tooth structure are two possible treatment modalities for such cases. Which one is best suited depends on the indications for each procedure. This study reports an orthodontic extrusion for the restoration of fractured upper canine. Preference of crown lengthening by orthodontic extrusion over surgical crown lengthening is clarified along the case discussion.

Background:The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTC have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention. The aim of this study is to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes. Methods: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity.Results: Among 25 candidate genes, ten (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions. Conclusion:Twelve genes predisposing to NMTC and their associated disease spectrums were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.