Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes.
Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes.
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DOI：
10.1186/1471-2164-13-719
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发表时间：
2012-12-22
期刊：
影响因子：
4.4
通讯作者：
Edwards PA
中科院分区：
文献类型：
--
作者：
Schulte I;Batty EM;Pole JC;Blood KA;Mo S;Cooke SL;Ng C;Howe KL;Chin SF;Brenton JD;Caldas C;Howarth KD;Edwards PA
最近发现，常见的上皮性癌症，如乳腺癌，具有与白血病相似的融合基因。在具有代表性的乳腺癌细胞系ZR-75-30中，我们通过分析基因组重排来寻找融合基因。我们首先通过分子细胞遗传学方法，结合阵列绘画和阵列CGH，分析了ZR-75-30基因组的重排，分辨率约为10kb。然后，我们将该图谱与通过对端测序确定的基因组连接进行了比较。通过阵列绘制和阵列CGH发现的大多数断点都是在成对末端测序中确定的——55%的未扩增断点和97%的扩增断点（因为它们由更多的序列读取表示）。通过分析，我们确定了9个表达的融合基因：APPBP2-PHF20L1、BCAS3-HOXB9、COL14A1-SKAP1、TAOK1-PCGF2、TIAM1-NRIP1、TIMM23-ARHGAP32、TRPS1-LASP1、USP32-CCDC49和ZMYM4-OPRD1。我们还确定了另外三个已被其他人描述的表达融合基因的基因组连接，BCAS3-ERBB2， DDX5-DEPDC6/DEPTOR和PLEC1-ENPP2。在这12个表达的融合基因中，9个在共扩增中。由于所使用技术的敏感性，我们估计这12个融合基因约占真实总数的三分之二。许多融合似乎是驱动突变。例如，PHF20L1、BCAS3、TAOK1、PCGF2和TRPS1在其他乳腺癌中融合。HOXB9和PHF20L1是在其他肿瘤中融合的基因家族成员。除了ERBB2， SKAP1是Src的接头，DEPTOR调控mTOR通路，NRIP1是雌激素受体的共调节因子。这是将经典分子细胞遗传学方法与测序相结合的首次乳腺癌基因组结构分析。配对端测序能够检测到几乎所有的断点，在那里有足够的读取深度。它支持了基因断裂和基因融合是乳腺癌中重要的突变类型的观点，一个典型的乳腺癌表达了许多融合基因。
It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements. We first analysed rearrangements of the ZR-75-30 genome, to around 10kb resolution, by molecular cytogenetic approaches, combining array painting and array CGH. We then compared this map with genomic junctions determined by paired-end sequencing. Most of the breakpoints found by array painting and array CGH were identified in the paired end sequencing—55% of the unamplified breakpoints and 97% of the amplified breakpoints (as these are represented by more sequence reads). From this analysis we identified 9 expressed fusion genes: APPBP2-PHF20L1, BCAS3-HOXB9, COL14A1-SKAP1, TAOK1-PCGF2, TIAM1-NRIP1, TIMM23-ARHGAP32, TRPS1-LASP1, USP32-CCDC49 and ZMYM4-OPRD1. We also determined the genomic junctions of a further three expressed fusion genes that had been described by others, BCAS3-ERBB2, DDX5-DEPDC6/DEPTOR and PLEC1-ENPP2. Of this total of 12 expressed fusion genes, 9 were in the coamplification. Due to the sensitivity of the technologies used, we estimate these 12 fusion genes to be around two-thirds of the true total. Many of the fusions seem likely to be driver mutations. For example, PHF20L1, BCAS3, TAOK1, PCGF2, and TRPS1 are fused in other breast cancers. HOXB9 and PHF20L1 are members of gene families that are fused in other neoplasms. Several of the other genes are relevant to cancer—in addition to ERBB2, SKAP1 is an adaptor for Src, DEPTOR regulates the mTOR pathway and NRIP1 is an estrogen-receptor coregulator. This is the first structural analysis of a breast cancer genome that combines classical molecular cytogenetic approaches with sequencing. Paired-end sequencing was able to detect almost all breakpoints, where there was adequate read depth. It supports the view that gene breakage and gene fusion are important classes of mutation in breast cancer, with a typical breast cancer expressing many fusion genes.
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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.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
30.8
作者：
Campbell, Peter J.;Stephens, Philip J.;Pleasance, Erin D.;O'Meara, Sarah;Li, Heng;Santarius, Thomas;Stebbings, Lucy A.;Leroy, Catherine;Edkins, Sarah;Hardy, Claire;Teague, Jon W.;Menzies, Andrew;Goodhead, Ian;Turner, Daniel J.;Clee, Christopher M.;Quail, Michael A.;Cox, Antony;Brown, Clive;Durbin, Richard;Hurles, Matthew E.;Edwards, Paul A. W.;Bignell, Graham R.;Stratton, Michael R.;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
影响因子：
1.9
作者：
Hampton OA;Koriabine M;Miller CA;Coarfa C;Li J;Den Hollander P;Schoenherr C;Carbone L;Nefedov M;Ten Hallers BF;Lee AV;De Jong PJ;Milosavljevic A
通讯作者：
Milosavljevic A