Datasets and metadata supporting the published article: Prevalence of Disease-Causing Genes in Japanese Patients with BRCA1/2-Wildtype Hereditary Breast and Ovarian Cancer Syndrome

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear.

In this study, the authors examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history.

Data access: Data supporting figures 2, 3, tables 1-5 and supplementary table 1, are publicly available in the figshare repository as part of this data record: Germline SNV/indel data are publicly available in ClinVar under the following ClinVar submission accession IDs: SCV001193462 – SCV001193759. The 298 ClinVar submissions can also be accessed here: re-sequencing data are available in the National Bioscience Database Centre (NBDC) under the dataset accession ID JGAS00000000224. Exome sequencing data are not publicly available in order to protect patient privacy, but can be accessed from the corresponding author, Dr. Seigo Nakamura (email:, on reasonable request.

Study approval and patient consent: Patients included in the study were from six academic and cancer hospitals in Japan: Showa University Hospital (Hatanodai, Tokyo), Cancer Institute Hospital (Ariake, Tokyo), St. Luke’s International Hospital (Akashi-cho, Tokyo), Shikoku Cancer Center (Minami-umemoto-cho, Matsuyama), Sagara Hospital (Matsubara-cho, Kagoshima), and Keio University Hospital (Shinano-cho, Tokyo). These institutions participated in the “Project for Development of Innovative Research on Cancer Therapeutics” (P-DIRECT; 2014–2015) research program, and in the succeeding “Project for Cancer Research and Therapeutic Evolution” (P-CREATE; 2016–2017) program, granted by the Japan Agency for Medical Research and Development (AMED). Sample acquisition and genetic analyses were approved by the institutional review board at each institution. After genetic counselling, written informed consent was obtained from all participants (probands or family members).

Study aims and methodology:

In this study, the authors aimed to identify the frequencies of germline variants in previously recognized causal genes for HBOC syndrome across 568 Japanese patients with wildtype (i.e., mutation-negative) BRCA1/2 genes and a strong family history. These classifications were associated with clinicopathological data, and were verified by comparing the identified alleles in our cohort against those in germline-variant databases and against genetic alterations in tumor specimens.

A total of 666 patients were recruited and underwent genetic counselling at one of six Japanese institutions mentioned above. Patients were classified into two groups: Group 1 patients (n = 230) were negative for BRCA1/2 mutations (BRCA1/2 wildtype, WT), whereas group 2 patients (n = 436) had not yet received BRCA1/2 genetic tests.

Group 2 patients were subjected to BRCA1/2 mutational analysis, of which 82 patients were positive for BRCA1/2 mutations and 16 were identified as having variants of unknown significance (VUS).

Germline DNA from a total of 568 BRCA1/BRCA2 WT, 27 BRCA1/BRCA2 mutation-positive and 10 VUS cases were rendered to exome sequencing analyses.

Experimental techniques including BRCA1/2 mutation test, blood, saliva and tumor sample acquisition, sample preparation for sequencing, library preparation and sequencing for exome analysis and germline variant analysis, are described in more detail in the published article.

Datasets supporting the figures and figures in the published article:

Data supporting figure 2: Clinicopathological_Info_Summary.xlsx in .xlsx file format (available in this figshare data record)

Data supporting figure 3: FisherTest_OtherFamilialBreastCancer.xlsx in .xlsx file format (available in this figshare data record)

Data supporting table 1: Japanese_HBOC_P_LP_Variants_DBInfo.xlsx (available in this figshare data record), Japanese_HBOC_Variants.xlsx (available in ClinVar as described in the Data access section), TR_SampleID_R[1/2].fastq.gz in .fastq file format (available from the NBDC repository as described in the Data access section), Ex_SampleID_R[1/2].fastq.gz in .fastq file format (not publicly available)

Data supporting table 2: FisherTest_NormalDB.xlsx in .xlsx file format (available in this figshare data record)

Data supporting tables 3-5: P_LP_Variants_Tumore_Info.xlsx in .xlsx file format (available in this figshare data record)

Data supporting supplementary table 1: 119HBOC_related_genes.xlsx in .xlsx file format (available in this figshare data record)