胃贲门腺癌中局灶扩增与染色体重排事件和不同预后相关。
Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma.
机构信息
State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key, Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, 450052, Zhengzhou, Henan, PR China.
Department of Immunology, Genetics and Pathology, Uppsala University, 75108, Uppsala, Sweden.
出版信息
Nat Commun. 2021 Nov 11;12(1):6489. doi: 10.1038/s41467-021-26745-3.
The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
在胃食管结合部腺癌（GCA）中，局灶扩增和额外染色体 DNA（ecDNA）的作用尚不清楚。在这里，我们鉴定了中国 GCA 患者样本中的频繁局灶扩增和 ecDNA，并发现 GCA 队列中的局灶扩增与染色体重排过程有关，并且可能是由于局部饮食习惯导致的累积 DNA 损伤所诱导。我们观察到致癌基因局灶扩增与预后之间存在多种相关性，其中 ERBB2 局灶扩增与预后呈正相关，而 EGFR 局灶扩增与预后呈负相关。来自 1668 例 GCA 患者的大规模 ERBB2 免疫组化结果表明，当 ERBB2 阳性患者的存活时间少于 2 年时，其生存概率低于 ERBB2 阴性患者，然而，当存活时间超过 2 年时，这种趋势相反。我们的观察表明，在 GCA 患者中，ERBB2 局灶扩增可能代表一个良好的预后标志物。
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