PALB2 mutations in high-risk women with breast or ovarian cancer.

Abstract

1527 Background: In Canada, genetic testing for BRCA1 and BRCA2 is available free of charge to women who meet eligibility criteria, based on personal and family history of cancer. Less than 10% of women are identified with a BRCA mutation, despite features of hereditary cancer. PALB2 has been identified as a moderate penetrance gene in various populations. In the current study, we examined the frequency of PALB2 mutations in women with breast or ovarian cancer who met criteria for genetic testing for BRCA1 and BRCA2and tested negative. Methods: DNA samples from women with breast or ovarian cancer, who met criteria for provincial BRCA1 and BRCA2 genetic testing and tested negative between the years of 2007 and 2014 were included in this study. All 13 coding exons of PALB2 plus 20 base pairs from the exon boundaries were amplified using Wafergen SmartChip technology. The amplified DNA were paired-end sequenced at 2x250 cycles using an Illumina MiSeq sequencer. Results: 2,225 women with breast cancer and 429 women with ovarian cancer were tested for PALB2 mutations. No PALB2 mutations were found in women with ovarian cancer. Seventeen deleterious PALB2 mutations were detected in women with breast cancer (0.8%). The frequency of PALB2 mutations was significantly higher in women with bilateral breast cancer (2.4%) compared to women with unilateral breast cancer (0.6%) (p = 0.01). There was no significant difference in age at diagnosis between those with and without a PALB2mutation (50.9 years vs 53.8 years; p = 0.34). Conclusions: Genetic testing for PALB2 should be considered for high-risk women with breast cancer, especially those who present with bilateral breast cancer. However, PALB2 does not appear to contribute to ovarian cancer which has implications for counselling women who are identified with a PALB2 mutation.