# Molecular Landscape of Metastatic Lung Adenocarcinoma in Bulgarian Patients—A Prospective Study

## TL;DR

This study characterizes the genetic mutations in lung cancer among Bulgarian patients, showing common mutations like TP53 and KRAS, and highlights the importance of personalized treatment.

## Contribution

The study provides the first detailed molecular profile of metastatic lung adenocarcinoma in Bulgarian patients.

## Key findings

- TP53 mutations were the most frequent (41.5%) in Bulgarian patients with lung adenocarcinoma.
- KRAS c.34G>T (p.Gly12Cys) mutations were found in 17.0% of the cohort.
- Over half of the patients had two or more gene mutations.

## Abstract

Lung adenocarcinoma exhibits a heterogeneous molecular landscape shaped by key oncogenic drivers and tumor suppressor gene alterations. Mutation frequencies vary geographically, influenced by genetic ancestry and environmental factors. However, the molecular profile of lung adenocarcinoma in Bulgarian patients remains largely uncharacterized. We conducted a prospective study of 147 Bulgarian patients with metastatic lung adenocarcinoma, analyzing clinicopathologic features and somatic mutation frequencies using next-generation sequencing. Key mutations and their prevalence were assessed and compared with published data from other populations. The cohort included predominantly male patients (68.0%) with a median age of 67 years. TP53 mutations were most frequent (41.5%), followed by EGFR alterations (19.0%) and KRAS c.34G>T (p.Gly12Cys) (17.0%). Over half of the patients (51.0%) harbored two or more gene mutations. Mutation frequencies aligned closely with European cohorts, exhibiting a lower prevalence of EGFR mutations compared to East Asian populations. This study characterizes the molecular landscape of lung adenocarcinoma in Bulgaria, highlighting the predominance of TP53 and KRAS mutations. The findings emphasize the need for comprehensive molecular profiling to inform targeted therapies and support precision oncology approaches tailored to the Bulgarian population. Further research is needed to validate these results and improve clinical outcomes.