Nobuyuki Susumu

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

A questionnaire survey of pharmacists regarding the clinical practice guidelines for the appropriate use of granulocyte-colony stimulating factors

BackgroundClinical practice guidelines should be user-friendly and confirming their penetration rate and compliance are critical.MethodsWe conducted a nationwide web-based questionnaire survey among pharmacists regarding the 2013 guidelines for the appropriate use of granulocyte-colony stimulating factors (G-CSFs) (version 2, published by the Japan Society of Clinical Oncology [JSCO]) between August 24 and September 6, 2015.ResultsA total of 301 pharmacists responded; 96.0% belonged to hospitals and were board-certified pharmacists in oncology pharmacy (nu2009=u2009133) and palliative pharmacy (nu2009=u200978). In addition, 61.5% of respondents (nu2009=u2009185) worked for designated cancer care hospitals. The observation that 75.7% of respondents knew that the JSCO guidelines are available on the internet indicated that several pharmacists used this guideline. A high degree of usability by pharmacists was also demonstrated, as 98.0% and 51.5% of respondents, respectively, agreed with the statements “it is useful for the work of pharmacists” and “it is referred to in the actual work of pharmacists”. However, more than half of the respondents (58.4%) agreed with the phrase “there are differences from the actual work of pharmacists”.ConclusionsTheir responses indicated that the respondents used the G-CSF guidelines and viewed them positively; however, the observation that about half of the respondents reported feeling that the guidelines do not match their current practice requires additional follow-up in future studies. The use of these guidelines should be routinely assessed in order to introduce novel cancer chemotherapy regimens and long-acting G-CSF in clinical practice.

Epimutation in DNA Mismatch Repair (MMR) Genes

Generally, disease susceptibility is determined based on changes not only in DNA sequen‐ ces but also in the activities of genes and chromosomal regions. Epigenetic regulation has attracted attention as a mechanism underlying changes of activities of genes and chromoso‐ mal regions. Epigenetic modification regulates gene activity and is essential for cell division and histogenesis. Genetically, phenotype diversity of identical cells is thought to be caused by differences in epigenetic profiles. Epimutations have also recently been recognized as the first step of tumorigenesis of cancers and are thought to be direct dispositions to cancers [1].