Detection of RAS and RAS-associated alterations in primary lung adenocarcinomas. A correlation between molecular...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Rat sarcoma (RAS) and associated pathways are crucial in lung cancer pathogenesis and targeted therapy development.
• The precise clinical significance of RAS pathways in lung cancer remains incompletely understood.
• Investigating molecular aberrations in RAS pathways is essential for advancing lung cancer treatment strategies.

Purpose of the Study:

• To investigate RAS-associated molecular aberrations in primary lung adenocarcinomas.
• To correlate these molecular findings with clinicopathological tumor characteristics.
• To provide a comprehensive molecular profile of RAS pathway alterations in lung adenocarcinoma.

Main Methods:

• Analysis of 220 surgically resected lung adenocarcinomas.
• Utilized a lung cancer molecular panel including next-generation sequencing (7 genes) and fluorescence in situ hybridization (3 genes).
• Examined mutations in KRAS, EGFR, BRAF, PIK3CA, NRAS, and ALK alterations.

Main Results:

• Overall molecular alterations detected in 65.00% (143/220) of tumors.
• KRAS (26.36%), EGFR (18.18%), BRAF (10.91%), PIK3CA (3.64%), NRAS (3.18%), and ALK (2.73%) alterations were identified.
• KRAS, BRAF, NRAS, and PIK3CA mutations were more frequent in smokers than previously reported. BRAF V600E mutations were common in female smokers; non-V600E mutations in both sexes with poorly differentiated tumors. PIK3CA mutations (p.E545K, p.E542K) occurred in poorly differentiated tumors.

Conclusions:

• RAS-associated molecular aberrations are prevalent in lung adenocarcinoma, especially in smokers.
• Specific mutation profiles correlate with distinct clinicopathological features, including smoking history and tumor differentiation.
• These findings enhance understanding of lung cancer molecular landscape and inform targeted therapeutic approaches.