The Data Use Ontology to streamline responsible access to human biomedical datasets.

Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.

Germline mutations of multiple breast cancer-related genes are differentially associated with triple-negative breast cancers and prognostic factors.

Genetic testing for BRCA1/2 mutations has become the standard clinical practice. Recent findings suggest the clinical significance of multigene panel testing of BRCA1/2 and other cancer-related genes. However, the clinical features of patients with breast cancer with germline mutations identified using multigene panels remain unclear. In this study, DNA samples from 583 Chinese women with breast cancer were subjected to target sequencing for 54 cancer-related genes using a pre-capture pooling method followed by next-generation sequencing. We identified 79 pathogenic germline mutations in 21 cancer-related genes. Forty-five patients (7.7%) harbored BRCA1/2 mutations, and 38 patients (6.5%) carried pathogenic mutations in the remaining 19 genes. PALB2 was the most commonly (1.2%) mutated gene other than BRCA1/2. Most of the identified pathogenic mutations were novel, suggesting mutation screening by using multigene panel testing is important particularly for non-European populations. Mutations in BRCA1/2 and the other cancer-related genes were differentially associated with clinical features. BRCA1 mutation carriers were strongly associated with triple-negative breast cancer (TNBC), whereas BRCA2 mutation carriers were not. Tumors in BRCA1-mutation carriers had a high histological grade. Patients with BRCA2-mutated breast cancers were likely to develop E-cadherin-negative tumors with bone metastases. Furthermore, mutations in PALB2 were strongly associated with TNBC. We demonstrated the usefulness of multigene panel testing and observed that a substantial proportion of patients with breast cancer had hereditary risk factors. Identifying differential associations between mutation status and clinical features will advance our understanding regarding the pathologies of this heterogeneous disease.

Exploration of intermediate-sized INDELs by next-generation multigene panel testing in Han Chinese patients with breast cancer.

Multigene panel testing via next-generation sequencing focuses on the detection of small-sized mutations, such as single nucleotide variants and short insertions and deletions (INDELs). However, intermediate-sized INDELs have not been fully explored due to technical difficulties. Here, we performed bioinformatics analyses to identify intermediate-sized INDELs in 54 cancer-related genes from 583 Han Chinese patients with breast cancer. We detected a novel deletion-insertion in a translational variant of PTEN (also known as PTENα) in one patient.

Concurrent isolated retroperitoneal HGSC and STIC defined by somatic mutation analysis: a case report.

BACKGROUND: Retroperitoneal high-grade serous carcinoma (HGSC) is extremely rare and the origin remains unclear. We present a case of retroperitoneal HGSC and coexisting serous tubal intraepithelial carcinoma (STIC), which is considered as the main origin of ovarian HGSC. We reviewed the available literature and discussed about the origin of this rare disease. CASE PRESENTATION: A 58-year-old female with a 93 × 65 × 62 mm-solid tumor with a cystic part was located immediately dorsal to the rectum underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and en bloc resection of the retroperitoneal tumor together with lower anterior resection of the rectum. Histological diagnosis was retroperitoneal HGSC and STIC at the right fallopian tube. Two deleterious somatic mutations in TP53 and BRCA2 genes were shared between retroperitoneal HGSC and STIC. CONCLUSIONS: In addition to clinical features in the previous reports, our genetic findings suggest the origin of retroperitoneal HGSC might be STIC.

Clonazepam use for prevention of acute and delayed vomiting induced by Cisplatin-based chemotherapy for lung cancer.

We investigated the efficacy of clonazepam as an antiemetic in cisplatin-based chemotherapy for lung cancer. Seven patients experienced cisplatin-induced vomiting despite antiemetic therapy including 5-hydroxytryptamine(3) (5-HT(3)) antagonist and dexamethasone. Therefore, the antiemetic therapy including clonazepam, 5-HT(3) antagonist and dexamethasone was subsequently explored in the next course for the same seven patients. We administered clonazepam (0.5 or 1.0 mg/kg) once a day orally for 5 d from day one prior to chemotherapy. The grade of delayed vomiting, evaluated according to Common Terminology Criteria for Adverse Events Version 3.0, in the courses of therapy with clonazepam was significantly lower than without clonazepam (p=0.013). The patients whose serum clonazepam concentrations were below the lower limit of detection (3.0 ng/ml) experienced vomiting in three of three courses, whereas the patients whose serum clonazepam concentrations were higher than 4.3 ng/ml experienced no vomiting in six of seven courses. We observed that the symptom of cisplatin-induced delayed vomiting is controlled with serum clonazepam levels in the order of 10.0 ng/ml.