Genomic Landscape Features of Minimally Invasive Adenocarcinoma and Invasive Lung Adenocarcinoma

TL;DR

This study compares the genomic differences between minimally invasive and invasive lung adenocarcinoma, finding distinct mutation patterns that suggest early versus late genetic changes in cancer progression.

Contribution

The study identifies specific genomic features distinguishing minimally invasive from invasive lung adenocarcinoma, highlighting early and late genetic events in tumor development.

Findings

ERBB2 mutations and RET fusions are early genomic events in lung adenocarcinoma.

TP53 and CDKN2A mutations, along with ALK fusions, occur later in tumor progression.

Genomic intratumor heterogeneity likely arises before invasive characteristics develop.

Abstract

Background
 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.

Methods
 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.

Results
 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 (
p
 < 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 (
p
 < 0.001). ERBB2 mutations were identified in 23 MIA patients (19.3%) and 20 IAC patients (6.6%) (
p
 < 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.

Conclusion
 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.

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