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Analysis of induced pluripotent stem cells from a BRCA1 mutant family

Abigail A. Soyombo; Yipin Wu; Lauren Kolski; Jonathan J. Rios; Dinesh Rakheja; Alice Chen; James Kehler; Heather Hampel; Alanna Coughran; Theodora S. Ross

(Profiled Authors: Dinesh Rakheja; Jonathan J Rios; Theodora S Ross)

Stem Cell Reports. 2013;1(4):336-349.

Abstract

Summary Understanding 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. © 2013 The Authors.

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