小柯机器人

英国Wellcome Sanger研究所Michael R. Stratton团队揭示八个国家发病率不同的食管鳞状细胞癌的突变特征。这一研究成果于2021年10月18日在线发表在国际学术期刊《自然—遗传学》上。

研究人员将突变特征分析与癌症流行病学相结合，来分析了来自八个国家的552个食道鳞状细胞癌（ESCC）基因组，这些国家的发病率各不相同。所有研究国家的突变特征都很相似。烟草、酒精、鸦片和种系变体的特定突变特征和ESCC风险因素之间的关联被确定，对突变负担的影响不大。研究人员没有发现表明外源性暴露能够解释ESCC发病率差异的突变特征证据。APOBEC（apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like）相关的突变特征单碱基替换（SBS）2和SBS13分别存在于88%和91%的病例中，平均占突变负担的25%，这表明APOBEC的激活是ESCC肿瘤发展中的一个关键步骤。

据悉，ESCC的发病率显示出显著的变化，而已知的生活方式和环境风险因素无法完全解释。有人推测，未知的外源性暴露可能是原因。

附：英文原文

Title: Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence

Author: Moody, Sarah, Senkin, Sergey, Islam, S. M. Ashiqul, Wang, Jingwei, Nasrollahzadeh, Dariush, Cortez Cardoso Penha, Ricardo, Fitzgerald, Stephen, Bergstrom, Erik N., Atkins, Joshua, He, Yudou, Khandekar, Azhar, Smith-Byrne, Karl, Carreira, Christine, Gaborieau, Valerie, Latimer, Calli, Thomas, Emily, Abnizova, Irina, Bucciarelli, Pauline E., Jones, David, Teague, Jon W., Abedi-Ardekani, Behnoush, Serra, Stefano, Scoazec, Jean-Yves, Saffar, Hiva, Azmoudeh-Ardalan, Farid, Sotoudeh, Masoud, Nikmanesh, Arash, Poustchi, Hossein, Niavarani, Ahmadreza, Gharavi, Samad, Eden, Michael, Richman, Paul, Campos, Lia S., Fitzgerald, Rebecca C., Ribeiro, Luis Felipe, Soares-Lima, Sheila Coelho, Dzamalala, Charles, Mmbaga, Blandina Theophil, Shibata, Tatsuhiro, Menya, Diana, Goldstein, Alisa M., Hu, Nan, Malekzadeh, Reza, Fazel, Abdolreza, McCormack, Valerie, McKay, James, Perdomo, Sandra, Scelo, Ghislaine, Chanudet, Estelle, Humphreys, Laura, Alexandrov, Ludmil B., Brennan, Paul, Stratton, Michael R.

Issue&Volume: 2021-10-18

Abstract: Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

DOI: 10.1038/s41588-021-00928-6

Source: https://www.nature.com/articles/s41588-021-00928-6

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