小柯机器人

染色体碎裂与循环重组驱动人类癌症中的癌基因扩增
2021-11-21 23:54

近日,德国科隆大学Matthias Fischer、Martin Peifer等研究人员合作发现,染色体碎裂与循环重组驱动人类癌症中的癌基因扩增。这一研究成果于2021年11月15日在线发表在国际学术期刊《自然—遗传学》上。

利用小儿肿瘤神经母细胞瘤的全基因组测序数据,研究人员发现了一种扩增类型,称为"地震式扩增",其特点是多重排和不连续的拷贝数水平。总的来说,地震式扩增发生在38种癌症类型的9.9%病例中(2,756例中的274例),并与大量增加的拷贝数和升高的癌基因表达有关。地震式扩增的发育重建显示了一个逐步演变的过程,首先是染色体脱落事件,然后是形成环状染色体外DNA,随后经历了反复的循环重组。由此产生的扩增子作为染色体外DNA环持续存在,或者已经重新整合到明显的肿瘤的基因组中。总之,这些数据表明,在相当一部分人类恶性肿瘤中,染色体缺失和循环重组的相继发生推动了肿瘤基因的扩增和过度表达。

据悉,癌症中复杂的基因组扩增演变背后的机制在很大程度上仍不清楚。

附:英文原文

Title: Chromothripsis followed by circular recombination drives oncogene amplification in human cancer

Author: Rosswog, Carolina, Bartenhagen, Christoph, Welte, Anne, Kahlert, Yvonne, Hemstedt, Nadine, Lorenz, Witali, Cartolano, Maria, Ackermann, Sandra, Perner, Sven, Vogel, Wenzel, Altmller, Janine, Nrnberg, Peter, Hertwig, Falk, Ghring, Gudrun, Lilienweiss, Esther, Sttz, Adrian M., Korbel, Jan O., Thomas, Roman K., Peifer, Martin, Fischer, Matthias

Issue&Volume: 2021-11-15

Abstract: The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. Using whole-genome sequencing data of the pediatric tumor neuroblastoma, we here identified a type of amplification, termed ‘seismic amplification’, that is characterized by multiple rearrangements and discontinuous copy number levels. Overall, seismic amplifications occurred in 9.9% (274 of 2,756) of cases across 38 cancer types, and were associated with massively increased copy numbers and elevated oncogene expression. Reconstruction of the development of seismic amplification showed a stepwise evolution, starting with a chromothripsis event, followed by formation of circular extrachromosomal DNA that subsequently underwent repetitive rounds of circular recombination. The resulting amplicons persisted as extrachromosomal DNA circles or had reintegrated into the genome in overt tumors. Together, our data indicate that the sequential occurrence of chromothripsis and circular recombination drives oncogene amplification and overexpression in a substantial fraction of human malignancies.

DOI: 10.1038/s41588-021-00951-7

Source: https://www.nature.com/articles/s41588-021-00951-7

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

分享到:

0