Genetic Alteration Profiling in North Macedonian Lung Cancer Patients.

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Lung cancer, including non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), has a poor prognosis due to late diagnosis and inefficient treatments.
• Developing targeted therapies requires identifying new oncogenes and thoroughly investigating known driver genes.

Purpose of the Study:

• To investigate the prevalence of alterations in eight key lung cancer genes: BRAF, EGFR, KRAS, ALK, ROS1, HER2, PD-L1, and PIK3CA.

Main Methods:

• Utilized real-time polymerase chain reaction (RT-PCR) for KRAS and EGFR mutations.
• Employed multiplex PCR and microarray hybridization for KRAS/BRAF/PIK3CA mutations.
• Conducted immunohistochemical analysis for ALK, HER2/NEU, ROS-1, and PD-L1 alterations.

Main Results:

• 36.65% of 603 patients (221) had at least one genetic alteration; 3.65% had multiple alterations.
• Identified mutations in KRAS (8.29%), EGFR (7.46%), PIK3CA (1.82%), and BRAF (0.66%).
• Detected PD-L1 overexpression (10.45%), ALK rearrangements (5.31%), and HER2/NEU expression (2.36%), with no ROS-1 rearrangements.

Conclusions:

• Comprehensive testing for somatic alterations in EGFR, BRAF, KRAS, and PIK3CA is vital for guiding lung cancer treatment decisions.
• Routine genetic profiling of lung cancers is recommended for efficient and cost-effective patient management.
• Establishing a thorough genetic profile aids in selecting appropriate targeted therapies and improving patient outcomes.