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用于单核苷酸水平染色体畸变研究的泌尿生殖系统癌症基因组组装资源。

Genome assembly resources of genitourinary cancers for chromosomal aberration at the single nucleotide level.

作者信息

Han Hyunho, Lee Hyung Ho, Kim Min Gyu, Shin Yoo Sub, Chung Jin Soo, Kim Jun

机构信息

Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

Center for Urologic Cancer, National Cancer Center, Goyang, Republic of Korea.

出版信息

Sci Data. 2025 Apr 1;12(1):550. doi: 10.1038/s41597-025-04801-7.

Abstract

Traditionally, the evolutionary perspective of cancer has been understood as gradual alterations in passenger/driver genes that lead to branching phylogeny. However, in cases of prostate adenocarcinoma and kidney renal cell carcinoma, macroevolutionary landmarks like chromoplexy and chromothripsis are frequently observed. Unfortunately, short-read sequencing techniques often miss these significant macroevolutionary changes, which involve multiple translocations and deletions at the chromosomal level. To resolve such genomic dark matters, we provided high-fidelity long-read sequencing data (78-92 Gb of ~Q30 reads) of six genitourinary tumour cell lines (one benign kidney tumour and two kidney and three prostate cancers). Based on these data, we obtained 12 high-quality, partially phased genome assemblies (Contig N50 1.85-29.01 Mb; longest contig 2.02-171.62 Mb), graph-based pan-genome variant sets (11.57 M variants including 60 K structural variants), and 5-methylcytosine sites (14.68%-27.05% of the CpG sites). We also identified several severe chromosome aberration events, which would result from chromosome break and fusion events. Our cancer genome assemblies will provide unprecedented resolution to understand cancer genome instability and chromosomal aberration.

摘要

传统上,癌症的进化观点被理解为过客基因/驱动基因的逐渐改变,从而导致分支系统发育。然而,在前列腺腺癌和肾细胞癌病例中,经常观察到诸如染色体重排和染色体碎裂等宏观进化标志。不幸的是,短读长测序技术常常遗漏这些涉及染色体水平上多个易位和缺失的重大宏观进化变化。为了解决此类基因组暗物质问题,我们提供了六种泌尿生殖系统肿瘤细胞系(一种良性肾肿瘤以及两种肾癌和三种前列腺癌)的高保真长读长测序数据(78 - 92 Gb的~Q30读段)。基于这些数据,我们获得了12个高质量的、部分定相的基因组组装结果(重叠群N50为1.85 - 29.01 Mb;最长重叠群为2.02 - 171.62 Mb)、基于图谱的泛基因组变异集(1157万个变异,包括6万个结构变异)以及5 - 甲基胞嘧啶位点(占CpG位点的14.68% - 27.05%)。我们还鉴定了一些严重的染色体畸变事件,这些事件是由染色体断裂和融合事件导致的。我们的癌症基因组组装将为理解癌症基因组不稳定性和染色体畸变提供前所未有的分辨率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac21/11962096/c76870440330/41597_2025_4801_Fig1_HTML.jpg

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