來源：生物谷 2014-11-04 13:39
2014年11月4日訊 /生物谷BIOON/ --昆士蘭州研究人員發(fā)現(xiàn)，突然的“染色體災(zāi)難”可能引發(fā)食道癌。分子生物科學(xué)研究所醫(yī)生Nic Waddell表示，這項(xiàng)研究是基于對22例食管腺癌（OAC）患者的全基因組測序所得出的。
在32％的OAC患者集體中都存在損傷DNA的突變，將導(dǎo)致高突變和基因組重排，Waddell博士說：我們在另一群101例患者中證實(shí)了這一發(fā)現(xiàn)。所有患者腫瘤細(xì)胞中都有遺傳DNA損壞的“足跡”。
項(xiàng)目負(fù)責(zé)人Andrew Barbour教授說：OAC患者亦有最差結(jié)果，只有14％的患者能存活5年。他說，當(dāng)染色體被破壞，可以以某種方式重新排列，導(dǎo)致一個(gè)特定的基因開啟或關(guān)閉，這樣的事件就會引發(fā)癌細(xì)胞發(fā)生連鎖反應(yīng)，促使癌癥發(fā)展。
去除腫瘤是研究者最大的希望，但只有不到50％患者會被及早診斷進(jìn)行手術(shù)治療。如果進(jìn)一步的研究能找出什么觸發(fā)了災(zāi)難性事件，就可以幫助找到新措施，可能會阻止腫瘤的發(fā)展。
食管癌患者數(shù)量在過去20年增加了一倍，并預(yù)計(jì)將在未來二十年再翻一番。（生物谷Bioon.com）
Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis
Hiroyasu Yamamoto, Evan G. Williams, Laurent Mouchiroud, Carles Cantó, Weiwei Fan, Michael Downes, Christophe Héligon, Grant D. Barish, Béatrice Desvergne, Ronald M. Evans et al.
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.
