Chromosome-breakage genomic instability and chromothripsis in breast cancer.
Chromosome-breakage genomic instability and chromothripsis in breast cancer.
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DOI：
10.1186/1471-2164-15-579
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发表时间：
2014-07-09
期刊：
影响因子：
4.4
通讯作者：
Basik M
中科院分区：
文献类型：
--
作者：
Przybytkowski E;Lenkiewicz E;Barrett MT;Klein K;Nabavi S;Greenwood CM;Basik M
染色体断裂，随后是错误的DNA修复，导致癌症中的基因扩增和缺失。然而，仅仅评估基因组变化、扩增和缺失的程度可能会降低通过阵列比较基因组杂交（阵列CGH）观察到的基因组数据的复杂性。我们在这里提出了一种新的方法来阵列CGH数据分析，其重点是假定的断点负责基因组内的重排。我们在29例乳腺癌高危患者的原发肿瘤中进行了阵列比较基因组杂交。在阵列CGH之前，根据倍性对样本进行流式分选以增加肿瘤细胞纯度。我们描述了染色体断裂的数量以及每个肿瘤中单个染色体的断裂模式。有不同的染色体断裂模式之间的3个临床亚型的乳腺癌，虽然最高密度的断裂发生在17号染色体在所有亚型，这表明一个特殊的倾向，该染色体断裂。我们还观察到，在41%的高危乳腺癌中，染色体断裂影响各种染色体。我们的研究结果为乳腺癌的基因组复杂性提供了新的见解。依赖于染色体断裂事件的基因组不稳定性不是随机的，靶向某些染色体明显多于其他染色体。我们报告了比以前在其他癌症中描述的更高比例的染色体断裂，这表明在单一灾难性事件中发生的大规模基因组重排可能会塑造许多乳腺癌基因组。本文的在线版本（doi：10.1186/1471 - 2164 - 15 - 579）包含补充材料，可供授权用户使用。
Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome. We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers. Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes. The online version of this article (doi:10.1186/1471-2164-15-579) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Rausch T;Jones DT;Zapatka M;Stütz AM;Zichner T;Weischenfeldt J;Jäger N;Remke M;Shih D;Northcott PA;Pfaff E;Tica J;Wang Q;Massimi L;Witt H;Bender S;Pleier S;Cin H;Hawkins C;Beck C;von Deimling A;Hans V;Brors B;Eils R;Scheurlen W;Blake J;Benes V;Kulozik AE;Witt O;Martin D;Zhang C;Porat R;Merino DM;Wasserman J;Jabado N;Fontebasso A;Bullinger L;Rücker FG;Döhner K;Döhner H;Koster J;Molenaar JJ;Versteeg R;Kool M;Tabori U;Malkin D;Korshunov A;Taylor MD;Lichter P;Pfister SM;Korbel JO
通讯作者：
Korbel JO
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：
64.5
作者：
Maher CA;Wilson RK
通讯作者：
Wilson RK
影响因子：
6.6
作者：
Kwei KA;Kung Y;Salari K;Holcomb IN;Pollack JR
通讯作者：
Pollack JR
影响因子：
20.3
作者：
Magrangeas, Florence;Avet-Loiseau, Herve;Minvielle, Stephane
通讯作者：
Minvielle, Stephane