Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.
Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.
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DOI：
10.1016/j.cell.2020.08.006
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发表时间：
2020-10-01
期刊：
影响因子：
64.5
通讯作者：
Imielinski M
中科院分区：
文献类型：
--
作者：
Hadi K;Yao X;Behr JM;Deshpande A;Xanthopoulakis C;Tian H;Kudman S;Rosiene J;Darmofal M;DeRose J;Mortensen R;Adney EM;Shaiber A;Gajic Z;Sigouros M;Eng K;Wala JA;Wrzeszczyński KO;Arora K;Shah M;Emde AK;Felice V;Frank MO;Darnell RB;Ghandi M;Huang F;Dewhurst S;Maciejowski J;de Lange T;Setton J;Riaz N;Reis-Filho JS;Powell S;Knowles DA;Reznik E;Mishra B;Beroukhim R;Zody MC;Robine N;Oman KM;Sanchez CA;Kuhner MK;Smith LP;Galipeau PC;Paulson TG;Reid BJ;Li X;Wilkes D;Sboner A;Mosquera JM;Elemento O;Imielinski M
癌症基因组通常具有数百个体细胞DNA重排连接点，其中许多不能容易地分类为简单（例如缺失）或复杂（例如染色体断裂）结构变体类别。应用一种新的基因组图计算范式来分析2，778个肿瘤全基因组序列的连接拷贝数（JCN）拓扑结构，我们发现了三种新的复杂重排现象：pyrgo，rigma和tyfonas。Pyrgo是低JCN重复的“塔”，与早期复制区域和超增强剂相关，在乳腺癌和卵巢癌中富集。Rigma包括在晚期复制脆性位点的低JCN缺失的“裂缝”，在胃肠道癌中富集。Tyfonas是高JCN连接的“台风”和富含表达的蛋白编码融合和断裂超突变的折回倒置，经常在肢端而不是皮肤黑色素瘤中发现。根据基因组图衍生的特征对肿瘤进行聚类，确定了与DNA修复缺陷和预后不良相关的亚组。
Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g. deletion) or complex (e.g. chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are “towers” of low-JCN duplications associated with early replicating regions and superenhancers, enriched in breast and ovarian cancers. Rigma comprise “chasms” of low-JCN deletions at late-replicating fragile sites, enriched in gastrointestinal carcinomas. Tyfonas are “typhoons” of high-JCN junctions and fold-back inversions enriched in expressed protein-coding fusions and breakend hypermutation, frequently found in acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
64.8
作者：
通讯作者：
--
核苷酸分辨率上杂合性丧失和单相表达的全基因组丧失的综合分析揭示了三阴性乳腺癌的途径中断。
影响因子：
7
作者：
Ha G;Roth A;Lai D;Bashashati A;Ding J;Goya R;Giuliany R;Rosner J;Oloumi A;Shumansky K;Chin SF;Turashvili G;Hirst M;Caldas C;Marra MA;Aparicio S;Shah SP
通讯作者：
Shah SP
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA