Institute for Clinical and Translational Research, Baylor College of Medicine, One Baylor Plaza, Mailstop: BCM451, Houston, TX, 77030, USA.
Sci Rep. 2024 Jun 3;14(1):12732. doi: 10.1038/s41598-024-63468-z.
Single nucleotide substitutions are the most common type of somatic mutations in cancer genome. The goal of this study was to use publicly available somatic mutation data to quantify negative and positive selection in individual lung tumors and test how strength of directional and absolute selection is associated with clinical features. The analysis found a significant variation in strength of selection (both negative and positive) among tumors, with median selection tending to be negative even though tumors with strong positive selection also exist. Strength of selection estimated as the density of missense mutations relative to the density of silent mutations showed only a weak correlation with tumor mutation burden. In the "all histology together" analysis we found that absolute strength of selection was strongly correlated with all clinically relevant features analyzed. In histology-stratified analysis selection was strongest in small cell lung cancer. Selection in adenocarcinoma was somewhat higher compared to squamous cell carcinoma. The study suggests that somatic mutation- based quantifying of directional and absolute selection in individual tumors can be a useful biomarker of tumor aggressiveness.
单核苷酸取代是癌症基因组中最常见的体细胞突变类型。本研究的目的是利用公开的体细胞突变数据来量化个体肺癌肿瘤中的负向和正向选择，并检验定向和绝对选择的强度与临床特征的相关性。分析发现，肿瘤之间的选择强度（负向和正向）存在显著差异，中位选择倾向于为负向，尽管也存在具有强烈正向选择的肿瘤。选择强度估计为错义突变相对于沉默突变的密度，与肿瘤突变负担仅显示出微弱的相关性。在“所有组织学综合”分析中，我们发现绝对选择强度与分析的所有临床相关特征都强烈相关。在组织学分层分析中，小细胞肺癌的选择最强。与鳞状细胞癌相比，腺癌的选择略高。该研究表明，基于体细胞突变的个体肿瘤定向和绝对选择的定量分析可能是肿瘤侵袭性的有用生物标志物。
