Department of Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Curr Oncol. 2022 Oct 4;29(10):7411-7419. doi: 10.3390/curroncol29100582.
TP53 is frequently mutated in solid tumors, but its basic mutation mapping is mixed, particularly in aggressive-stage lung cancer.
We curated a total of 139 advanced non-small cell lung cancer (NSCLC) patients who harbored wild-type TP53 (TP53wt) or mutated TP53 (TP53mut) based on next-generation sequencing (NGS) to analyze multiple-dimensional data types, including tumor mutation burden (TMB), programmed death receptor ligand 1 (PD-L1) expression, co-mutant alterations, hotspot mutations distribution, and therapy response.
TP53 was evident in 125 mutations and significantly associated with male sex, adenocarcinoma differentiation, smoking history, PD-L1 tumor proportion score, and TMB level. The most frequent mutations were distributed on exon 8, but there were no distinct hotspot mutations. After outlining the co-mutation genes, it is interesting to note that DNA damage repair (DDR) genes were frequent alterations in the mutated TP53 cohort. Even though there was no significant difference between the TP53wt and TP53mut cohorts on therapy response, patients with nucleotide variation in G>T achieved a relatively higher durable clinical benefit (DCB) rate.
This real-world retrospective study suggests that molecular stratification on the basis of TP53 mutations should be deeply explored for NSCLC to optimize and modify clinical therapy choices.
TP53 在实体瘤中经常发生突变，但基本突变图谱较为混杂，尤其是在侵袭性肺癌中。
我们共对 139 例携带野生型 TP53（TP53wt）或突变型 TP53（TP53mut）的晚期非小细胞肺癌（NSCLC）患者进行了下一代测序（NGS），以分析多种维度的数据类型，包括肿瘤突变负荷（TMB）、程序性死亡受体配体 1（PD-L1）表达、共突变改变、热点突变分布和治疗反应。
TP53 有 125 个突变，与男性、腺癌分化、吸烟史、PD-L1 肿瘤比例评分和 TMB 水平显著相关。最常见的突变分布在外显子 8，但没有明显的热点突变。在概述共突变基因后，有趣的是，在突变型 TP53 组中，DNA 损伤修复（DDR）基因是频繁的改变。尽管在治疗反应方面，TP53wt 和 TP53mut 两组之间没有显著差异，但在 G>T 核苷酸变异的患者中，相对较高的持久临床获益（DCB）率。
这项真实世界的回顾性研究表明，基于 TP53 突变的分子分层应该在 NSCLC 中进行深入探索，以优化和修改临床治疗选择。
