SummaryUnderstanding BRCA1 mutant cancers is hampered by difficulties in obtaining primary cells from patients. We therefore generated and characterized 24 induced pluripotent stem cell (iPSC) lines from fibroblasts of eight individuals from a BRCA1 5382insC mutant family. All BRCA1 5382insC heterozygous fibroblasts, iPSCs, and teratomas maintained equivalent expression of both wild-type and mutant BRCA1 transcripts. Although no difference in differentiation capacity was observed between BRCA1 wild-type and mutant iPSCs, there was elevated protein kinase C-theta (PKC-theta) in BRCA1 mutant iPSCs. Cancer cell lines with BRCA1 mutations and hormone-receptor-negative breast cancers also displayed elevated PKC-theta. Genome sequencing of the 24 iPSC lines showed a similar frequency of reprogramming-associated de novo mutations in BRCA1 mutant and wild-type iPSCs. These data indicate that iPSC lines can be derived from BRCA1 mutant fibroblasts to study the effects of the mutation on gene expression and genome stability.

Background Targeted prostate biopsies are changing the landscape of prostate cancer (PCa) diagnosis with the degree of suspicion on multiparametric MRI (mpMRI) being a strong predictor of targeted biopsy outcome. Data regarding the rate and potential causes of false-negative magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy in patients with highly suspicious mpMRI findings are lacking. Objectives To determine the rate of clinically significant PCa detection in repeat targeted biopsy or surgery in patients with highly suspicious mpMRI findings and an initial negative MRI-TRUS fusion targeted biopsy. Materials and Methods In this single center, retrospective study of prospectively generated data, men with highly suspicious lesions (Likert 5 score) on mpMRI and an initial negative MRI-TRUS fusion targeted biopsy were reviewed. The rate of PCa detection in a subsequent MRI-TRUS fusion targeted biopsy or radical prostatectomy was determined. Tumors in the intermediate and high risk groups according to the National Comprehensive Cancer Network criteria were considered clinically significant. Results 32 men with 38 Likert 5 lesions were identified. Repeat targeted biopsy or surgery detected cancer in 42% (16/38) of the Likert 5 lesions with initial negative targeted biopsy. Most of these cancers were intermediate (69%; 11/16) or high risk (25%; 4/16) tumors. Conclusion A negative round of targeted biopsies does not exclude clinically significant PCa in men with highly suspicious mpMRI findings. Patients with imaging-pathology disagreement should be carefully reviewed and considered for repeat biopsy or strict surveillance.