Analysis of induced pluripotent stem cells from a BRCA1 mutant family.
Analysis of induced pluripotent stem cells from a BRCA1 mutant family.
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DOI：
10.1016/j.stemcr.2013.08.004
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发表时间：
2013
影响因子：
5.9
通讯作者：
Ross, Theodora S.
中科院分区：
文献类型：
--
作者：
Soyombo, Abigail A.;Wu, Yipin;Kolski, Lauren;Rios, Jonathan J.;Rakheja, Dinesh;Chen, Alice;Kehler, James;Hampel, Heather;Coughran, Alanna;Ross, Theodora S.
从患者身上获得原代细胞的困难阻碍了对BRCA1突变癌症的了解。因此，我们从BRCA1 5382insC突变家族的8个个体的成纤维细胞中产生并鉴定了24个诱导多能干细胞（iPSC）系。所有BRCA1 5382insC杂合成纤维细胞、iPSCs和畸胎瘤均保持野生型和突变型BRCA1转录本的等量表达。虽然BRCA1野生型和突变型iPSCs之间的分化能力没有差异，但BRCA1突变型iPSCs中蛋白激酶C-theta （PKC-theta）升高。具有BRCA1突变和激素受体阴性乳腺癌的癌细胞系也表现出PKC-theta升高。24个iPSC系的基因组测序显示，BRCA1突变型和野生型iPSC中重编程相关的新生突变频率相似。这些数据表明，可以从BRCA1突变成纤维细胞中获得iPSC系，以研究该突变对基因表达和基因组稳定性的影响。从BRCA1突变家族中获得了诱导多能干细胞（iPSC）系，与原成纤维细胞系相比，iPSC系中BRCA1水平升高，突变iPSC和er阴性乳腺癌中蛋白激酶C-theta水平升高，仅在1个BRCA1突变家族中发现了新生突变增加，从BRCA1突变家族中产生了24个诱导多能干细胞（iPSC）系。蛋白激酶C-theta （PKC-theta）在BRCA1突变体中与野生型iPSC系相比升高。PKC-theta在er阴性乳腺癌中也有所增加。利用每位患者的淋巴母细胞、成纤维细胞和iPSCs的基因组序列进行生物信息学筛选，鉴定出与重编程相关的新生突变。在BRCA1突变型iPSC系中有1个发现突变数增加，而在野生型iPSC系中没有发现突变数增加。
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. Induced pluripotent stem cell (iPSC) lines from a BRCA1 mutant family were made BRCA1 was elevated in iPSC lines compared with progenitor fibroblast lines Protein kinase C-theta was elevated in mutant iPSCs and ER-negative breast cancer Increased de novo mutations were found in only one BRCA1 mutant iPSC line Twenty-four induced pluripotent stem cell (iPSC) lines were generated from a BRCA1 mutant family. Protein kinase C-theta (PKC-theta) was elevated in BRCA1 mutant compared to wild-type iPSC lines. PKC-theta was also increased in ER-negative breast cancers. A bioinformatic filter using the genome sequence of lymphoblasts, fibroblasts, and iPSCs from each patient identified reprogramming-associated de novo mutations. Increased mutation numbers were found in one of the BRCA1 mutant iPSC lines and none of the wild-type iPSC lines.
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影响因子：
56.9
作者：
FUTREAL, PA;LIU, QY;WISEMAN, R
通讯作者：
WISEMAN, R
影响因子：
8
作者：
Belguise, K.;Milord, S.;Chalbos, D.
通讯作者：
Chalbos, D.
影响因子：
4.8
作者：
Horwitz, AA;Sankaran, S;Parvin, JD
通讯作者：
Parvin, JD
BRCA1连接乳腺癌中雌激素受体α缺乏症的分子基础。
DOI：
10.1093/jnci/djm207
发表时间：
2007-11-21
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Hosey AM;Gorski JJ;Murray MM;Quinn JE;Chung WY;Stewart GE;James CR;Farragher SM;Mulligan JM;Scott AN;Dervan PA;Johnston PG;Couch FJ;Daly PA;Kay E;McCann A;Mullan PB;Harkin DP
通讯作者：
Harkin DP
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz