Disease Spectrum of Breast Cancer Susceptibility Genes.

BACKGROUND: Pathogenic 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. METHODS: Twelve 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. RESULTS: Forty-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. CONCLUSION: This 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.

Disease spectrum of gastric cancer susceptibility genes.

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 gene-disease associations for clinicians. 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. Out of 27 candidate genes, 13 were identified as gastric cancer susceptibility genes (APC, ATM, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH-Biallelic, PALB2, SMAD4, and STK11). A total of 145 gene-disease associations (with 45 unique diseases) were found to be associated with these 13 genes. Other gastrointestinal cancers were prominent among identified associations, with 11 of 13 gastric cancer susceptibility genes also associated with colorectal cancer, eight genes associated with pancreatic cancer, and seven genes associated with small intestine cancer. Gastric cancer susceptibility genes are frequently associated with other diseases as well as gastric cancer, with potential implications for how carriers of these genes are screened and managed. Unfortunately, commonly used genetic resources provide heterogeneous information with regard to these genes and their associated diseases, highlighting the importance of developing guides for clinicians that integrate data across available resources and the medical literature.

Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.

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 NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention. OBJECTIVE: The aim of this study was 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, 10 (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 spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.

Diffused mixed B-cell non-Hodgkin lymphoma of mandible.

Lymphomas are the third-most common cancer of the oral cavity after squamous cell carcinomas and salivary gland tumors. It is characterized by proliferation of lymphoid cells and their precursor. Diffuse B-cell non-Hodgkin lymphoma is the most common histological type of lymphoma in the head-and-neck region and most commonly affects older men in their seventh decade of life.