The Unique Genetic Mutation Characteristics Based on Large Panel Next-Generation Sequencing (NGS) Detection in...

Area of Science:

• Oncology
• Genomics
• Medical Diagnostics

Background:

• Increasing detection of multiple primary lung cancers (MPLC) due to advances in multislice spiral computed tomography (CT).
• MPLC presents unique genetic mutation characteristics distinct from advanced lung cancer.
• MPLC typically exhibits a low tumor mutation burden (TMB).

Purpose of the Study:

• To analyze the gene mutation characteristics of multiple primary lung cancers (MPLC).
• To utilize large panel next-generation sequencing (NGS) assays for comprehensive genetic profiling of MPLC.
• To investigate the clinical implications of specific gene mutations in MPLC.

Main Methods:

• Surgical specimens from 36 MPLC patients treated between Jan 2020 and Dec 2021 were analyzed.
• Large panel next-generation sequencing (NGS) assays targeting 425 tumor-associated genes were performed on 114 nodules.
• Statistical analysis was conducted to identify significant gene mutation patterns and their correlation with clinicopathological features.

Main Results:

• Epidermal growth factor receptor (EGFR) mutations were most frequent (55.3%), followed by ERBB2 (9.6%), BRAF (8.8%), and KRAS (8.8%).
• Specific mutations included ERBB2 Y772_A775dup (73%), KRAS G12C (18%), and BRAF V600E (10%).
• AT-rich interaction domain 1A (ARID1A) mutations were significantly higher in invasive adenocarcinomas with solid/micro-papillary components (p=0.008).
• The median tumor mutation burden (TMB) was low (1.1 MUTS/Mb).
• 97.2% of MPLC patients harbored driver gene mutations, with 47% exhibiting co-mutations, predominantly in EGFR, KRAS, ERBB2, and TP53.

Conclusions:

• MPLC exhibits unique genetic features and a generally low TMB.
• Comprehensive NGS is valuable for MPLC diagnosis and treatment guidance.
• ARID1A enrichment in specific invasive adenocarcinoma subtypes suggests potential for poor prognosis in these MPLC patients.