Zhang Wei, Xu Hui, Tang Ning, Han Shuang, Shu Hongyan
Department of Thoracic Surgery, Zibo Municipal Hospital, Zibo, Shandong, China.
Department of Anesthesiology, Zibo Municipal Hospital, Zibo, Shandong, China.
Glob Med Genet. 2024 Sep 19;11(4):312-318. doi: 10.1055/s-0044-1791198. eCollection 2024 Dec.
The widespread implementation of computed tomography has significantly increased the detection of small pulmonary nodules, including atypical adenomatous hyperplasia, minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). Few studies have focused on the genomic differences between MIA and IAC. We retrospectively analyzed patients with lung adenocarcinoma (LUAD) who underwent surgery from January 2020 to December 2023. Patients were categorized into MIA and IAC groups. The mutation status of common driver genes was assessed using next-generation sequencing. A total of 422 LUAD patients were included in the study, comprising 119 MIA cases and 303 IAC cases. MIA patients were younger and predominantly female compared with IAC patients. EGFR mutations were detected in 251 patients (59.5%), with the frequency of EGFR mutations increasing from 37.0% in MIA to 68.3% in IAC ( < 0.001). TP53 mutations were found in 108 patients (25.6%), with 7 patients (5.9%) in MIA and 101 patients (33.3%) in IAC ( < 0.001). ERBB2 mutations were identified in 23 MIA patients (19.3%) and 20 IAC patients (6.6%) ( < 0.001). Additionally, CDKN2A mutations were detected in 23 IAC patients (7.6%), while no mutations in this gene were found in the MIA group. Moreover, ALK and RET gene fusions were identified in 11 patients, respectively. ERBB2 mutations and RET fusions are early genomic events in LUAD, while TP53 and CDKN2A mutations and ALK fusions occur later. Genomic intratumor heterogeneity likely arises early, before invasive characteristics develop.
计算机断层扫描的广泛应用显著提高了对小肺结节的检测率，包括非典型腺瘤样增生、微浸润腺癌（MIA）和浸润性腺癌（IAC）。很少有研究关注MIA和IAC之间的基因组差异。
我们回顾性分析了2020年1月至2023年12月接受手术的肺腺癌（LUAD）患者。患者被分为MIA组和IAC组。使用下一代测序评估常见驱动基因的突变状态。
该研究共纳入422例LUAD患者，其中119例为MIA病例，303例为IAC病例。与IAC患者相比，MIA患者更年轻，且以女性为主。251例患者（59.5%）检测到EGFR突变，EGFR突变频率从MIA组的37.0%增加到IAC组的68.3%（P<0.001）。108例患者（25.6%）发现TP53突变，MIA组有7例（5.9%），IAC组有101例（33.3%）（P<0.001）。23例MIA患者（19.3%）和20例IAC患者（6.6%）检测到ERBB2突变（P<0.001）。此外，23例IAC患者（7.6%）检测到CDKN2A突变，而MIA组未发现该基因突变。此外，分别在11例患者中鉴定出ALK和RET基因融合。
ERBB2突变和RET融合是LUAD中的早期基因组事件，而TP53和CDKN2A突变以及ALK融合发生较晚。基因组肿瘤内异质性可能在侵袭性特征出现之前就已早期出现。
