Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing.
Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing.
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DOI：
10.1186/1471-2164-14-165
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发表时间：
2013-03-12
期刊：
影响因子：
4.4
通讯作者：
Sjöblom T
中科院分区：
文献类型：
--
作者：
Jiao X;Hooper SD;Djureinovic T;Larsson C;Wärnberg F;Tellgren-Roth C;Botling J;Sjöblom T
乳腺癌基因组中常见的染色体重排形式有缺失、插入、倒位和易位，这些重排中的一部分可能在肿瘤的发生中发挥重要作用。为了确定新的体细胞染色体重排，我们用长插入配对大规模平行测序的方法确定了15个激素受体阴性的乳腺肿瘤的基因组结构。我们鉴定和验证了40个体细胞结构改变，包括DDX10和SKA3基因之间的反复融合和涉及EPHA5基因的易位。其他重排被发现影响涉及表观遗传调节、有丝分裂和信号转导的途径中的基因，强调了它们在乳腺肿瘤发生中的潜在作用。RNA干扰抑制5个候选基因(DDX10、SKA3、EPHA5、cltc和tnik)可抑制乳腺癌细胞的生长。此外，乳腺癌细胞中DDX10的下调会导致核形态的凋亡频率增加。利用全基因组配对测序和RNA干扰分析，我们在乳腺癌基因组中发现了一些新的基因重排，并确定了DDX10、SKA3、EPHA5、Cltc和tnik是影响乳腺癌细胞生长和增殖的潜在癌症基因。
Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C