209P - Molecular atlas of copy number variation(CNV) in lung cancer with brain metastases

Background

Patients (pts) with lung cancer had high rates of brain metastasis (BM). Genetic alterations were associated with the metastatic spread of lung cancer cells in recent study, lung cancer driver genes, such as EGFR, ALK, and RET are risk factors for brain metastasis in advanced lung cancer pts. The number of CNV regions was markedly higher in the secondary metastatic tumor than the primary tumor in the lung. However, the precise mechanisms in BM were still unclear. In this study, we explored the clinical and molecular features of lung cancer with brain metastases in Chinese real word.

Methods

This study retrospectively analyzed the genomic alteration of Chinese lung cancer with brain metastases pts during 2019-2022. Next-generation sequencing (NGS) was performed to detect gene mutations in tumor. Lung cancer driver genes set, as EGFR, ALK, ROS1, BRAF, ERBB2, MET, KRAS and RET were evaluated in those pts.

Results

193 lung cancer with brain metastases pts were enrolled. Male:Female ratio: 128:65. Median age 61 years(Min-Max: 38-78). 79% of pts had CNV, and tumors with CNV had higher TMB values than those without CNV (7.7 vs. 2.8, p<0.001). The top3 amplification genes were: EGFR(n=25), MYC(n=11), ERBB2(n=10), and the three most frequently deletion genes were: CDKN2A (n=69), CDKN2B (n=69), PTEN (n=15). Among pts with TMB≥10, the proportion of pts with CNV was higher than that of pts without CNV (24% vs. 5%, χ2=7.22, p < 0.05). The numbers of pts with driver gene mutation and pts without driver gene mutation were 145 and 48, respectively, and there was no significant difference in age between the two groups. Pts with CNV and no driver gene mutation had higher TMB values (average TMB=9.6). The proportion of pts that carrying CNV in driver gene mutation tumors was similar to those without driver gene mutation (82% vs. 68%).

Conclusions

79% of pts with brain metastases had CNV. The top3 amplification genes were: EGFR, MYC, ERBB2, and the three most frequently deletion genes were: CDKN2A, CDKN2B, PTEN. The proportion of pts that carrying CNV in driver gene mutation tumors was similar to those without driver gene mutation. Pts with CNV and no driver gene mutation had higher TMB values, indicating the pts may have more clinical benefits from immunotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Xianfeng Zhang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.