title: Analysis of induced pluripotent stem cells from a BRCA1 mutant family.
abstract: 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.
authors: Department of Internal Medicine, High Risk Cancer Genetics Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Abigail A
authors: AA
authors: Soyombo
authors: Yipin
authors: Y
authors: Wu
authors: Lauren
authors: L
authors: Kolski
authors: Jonathan J
authors: JJ
authors: Rios
authors: Dinesh
authors: D
authors: Rakheja
authors: Alice
authors: A
authors: Chen
authors: James
authors: J
authors: Kehler
authors: Heather
authors: H
authors: Hampel
authors: Alanna
authors: A
authors: Coughran
authors: Theodora S
authors: TS
authors: Ross
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015894:Genome, Human; D006579:Heterozygote; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D000074121:Protein Kinase C-theta; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013724:Teratoma / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D007527:Isoenzymes; D012333:RNA, Messenger; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta