Utility of combined annotation‐dependent depletion (CADD) score was recently reported to rank pathogenicity as C‐scores ranging 1‐99 for both confirmed deleterious mutation. Using C‐scores for BRCA1/2 variants, we tried to constitute the classification system for variant of uncertain significance (VUS), which had been a major problem of genetic testing for hereditary breast and/or ovarian cancer. We analyzed BRCA1/2 genes for 283 patients with breast and/or ovarian cancer. The deleterious mutation and missesne mutations, minor variant, and wild type of BRCA1 and ‐2 were 5, 27, 251 and 15, 85, 183, respectively. Meanwhile, the variants with C‐score ≥10 were involved in 19/283 (6.7%) in BRCA1 and 34/283 (12%) in BRCA2. All deleterious mutations were included in this group. Frequency of personal history and family history of ovarian cancer were significantly high, and frequency of serous adenocarcinoma of ovary and triple negative breast cancer was relatively high in the group with deleterious mutations. Similar findings were seen in patients with variants of C‐score ≥10. According to the C‐score and population frequency, we could define VUS for 11 patients out of 283 patients (3.9 CADD is useful to classify the variant of BRCA1/2 and selecting the patient who needs further segregation studies.

Aim: The purpose of this study was to identify the competencies of genetic nursing practise required for general and genetic nurses. Methods: We conducted a four-stage survey using a Delphi process. We conducted an interview with 27 nurses who were involved in genetics-related care and extracted 89 items in seven categories. In the second survey, we mailed a questionnaire to 20 experts in genetics. In the third and fourth surveys, we asked 491 health-care providers, including nurses and physicians, who were involved in genetics-related care and agreed to participate in the study at 113 institutions in 40 prefectures. The respondents were asked to choose one of three options in each of 89 items: "A: General nurse's role", "B: Genetic nurse's role", and "C: Not appropriate as the nurse's role". The data were collected from August 2000 to March 2001. There were 295 final subjects, and the response rate was 60%. Results: The competencies required for general nurses were identified as "living support", "psychological support", and "identification of the client's wishes", while those required for genetic nurses were "provision and exchange of accurate genetic information", "referral to and collaboration with other organisations", and "client support to understand disease." Conclusions: These results suggest a direction for genetic nursing curricula. It is our challenge to incorporate genetics into the education programming.

These data indicate that the currently available preventive measures and/or counseling system may not be sufficient enough to convince the high risk population to receive the genetic testing or to overcome the prejudice in non-urban area in Japan, even if served free.

Abstract. Partner and localizer of breast cancer 2 (PALB2) was identified as a moderate-risk gene of breast and pancreas cancer. The present authors previously reported that no PALB2 germline mutations with a deleterious frameshift or stop codons were identified in 155 Japanese patients with breast and/or ovarian cancer who were estimated to be at risk of hereditary cancer, according to the National Comprehensive Cancer Network (NCCN) criteria. In the present study, one patient with a deleterious mutation of PALB2 (c. 2834+2 T>C) has been identified from a study of an additional 128 cases. Therefore, the prevalence of PALB2 among Japanese patients is now estimated to be 0.35% (1/283). The proband was a 63-year-old woman with bilateral breast cancer, although she had experienced no other cancers. The proband had two elder sisters, the eldest of whom died from pancreatic cancer at 60 years of age. The proband's 40-year-old daughter was affected, but did not show any malignancies. There are only a few reports concerning PALB2 mutations in Japan. To the best of our knowledge, this is the first case study to reveal the significance of DNA-repair genes in the development of malignancies in Japanese patients with breast cancer. IntroductionThe significance of the breast cancer 1 (BRCA1) and BRCA2 mutations in familial breast and ovarian cancer has been well established (1,2). However, the mutations of these genes are estimated to cause, at most, 20-30% of cases of hereditary breast cancer (3). The present authors studied the BRCA1/2 mutations in 191 patients in a previous study, but the prevalence was shown to be unexpectedly low (4,5). In fact, it was only 7% among the analyzed patients who had a family history of breast cancers.Partner and localizer of BRCA2 (PALB2) was identified as a moderate-risk gene in breast and pancreas cancer (6). PALB2 is located on chromosome 16p12.2 containing 13 exons and 12 introns, and is involved in BRCA2-associated pathways (6). Recently, Antoniou et al (7) reported that PALB2 carriers have a high risk of developing breast cancer, and concluded that the cumulative risk of mutation carrier was 34% by the age of 70 in their prospective follow-up study on 154 families.The prevalence of the PALB2 mutation was reported to be 1.2-3.4% in European countries, whereas it is very rare in Asian countries (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). To the best of our knowledge, no study has been performed that has identified the PALB2 deleterious mutation in Japanese patients with breast cancer. From our first cohort data, no deleterious PALB2 mutations were identified in 155 patients with breast and/or ovarian cancer who were estimated to be at risk of hereditary cancer according to the National Comprehensive Cancer Network (NCCN) criteria (19). In the present case study, an additional 128 cases having breast and/or ovarian cancer were studied, and the case of a patient with bilateral breast cancer is presented who harbors the deleterious mutation in PALB2. Factoring in the first cohort of 155 c...

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