Wang Jialiang, Guo Chang, Wang Jiexiao, Zhang Xiaopeng, Qi Jian, Huang Xiang, Hu Zongtao, Wang Hongzhi, Hong Bo
School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences (CAS), Hefei, China.
Cancer Control. 2025 Jan-Dec;32:10732748241307363. doi: 10.1177/10732748241307363.
and mutations are frequently detected in lung adenocarcinoma (LUAD). Tumor mutational signature (TMS) determination is an approach to identify somatic mutational patterns associated with pathogenic factors. In this study, through the analysis of TMS, the underlying pathogenic factors of LUAD with and mutations were traced.
This was a retrospective study. TMS of LUAD with and mutations from the TCGA, OncoSG, and MSK datasets was determined by two bioinformatics tools, namely the "MutationalPatterns" and "FitMS" packages. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) of LUAD clinical specimens was analyzed using capillary electrophoresis.
In LUAD with mutations, TMS analysis indicated that the smoking-related SBS4 signature was enriched. For LUAD with L858R mutation, the smoking-related SBS4 signature was enriched in the Western population from the TCGA database; however, the smoking-related SBS4 signature was not obvious in Asian LUAD patients. LUAD with exon19 deletion (19Del) exhibited stronger SBS15 signature, which was related to defective DNA mismatch repair. Capillary electrophoresis analysis showed that an EMAST locus was frequently instable in LUAD with 19Del. Different from the Western population, Asian LUAD patients with mutations exhibited the enrichment of SBS1, SBS2, and SBS13 signatures, which were associated with the endogenous mutation process of cytidine deamination.
TMS analysis reveals that smoking is associated with LUAD with mutations. Defective DNA mismatch repair and endogenous cytidine deamination are associated with LUAD with mutations, especially for the 19Del. The endogenous mutational process is stronger in Asian LUAD patients than Western LUAD patients.
EGFR和KRAS突变在肺腺癌（LUAD）中经常被检测到。肿瘤突变特征（TMS）测定是一种识别与致病因素相关的体细胞突变模式的方法。在本研究中，通过TMS分析，追踪了具有EGFR和KRAS突变的LUAD的潜在致病因素。
这是一项回顾性研究。使用两种生物信息学工具，即“MutationalPatterns”和“FitMS”软件包，确定来自TCGA、OncoSG和MSK数据集的具有EGFR和KRAS突变的LUAD的TMS。使用毛细管电泳分析LUAD临床标本中选定四核苷酸重复序列处的微卫星改变升高（EMAST）。
在具有EGFR突变的LUAD中，TMS分析表明与吸烟相关的SBS4特征富集。对于具有EGFR L858R突变的LUAD，来自TCGA数据库的西方人群中与吸烟相关的SBS4特征富集；然而，在亚洲LUAD患者中，与吸烟相关的SBS4特征并不明显。具有EGFR外显子19缺失（19Del）的LUAD表现出更强的SBS15特征，这与DNA错配修复缺陷有关。毛细管电泳分析表明，在具有EGFR 19Del的LUAD中，一个EMAST位点经常不稳定。与西方人群不同，具有EGFR突变的亚洲LUAD患者表现出SBS1、SBS2和SBS13特征的富集，这些特征与胞苷脱氨的内源性突变过程相关。
TMS分析表明吸烟与具有EGFR突变的LUAD相关。DNA错配修复缺陷和内源性胞苷脱氨与具有KRAS突变的LUAD相关，特别是对于KRAS 19Del。亚洲LUAD患者的内源性突变过程比西方LUAD患者更强。
