Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4

摘要: Background Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling a large cohort to uncover other potential this pathway could contribute tumorigenesis. Methodology/Principal Findings We analyzed genomic DNA from total 261 resected, clinically annotated non-small cell cancer (NSCLC) specimens. The coding sequences 39 were screened for via high-throughput dideoxynucleotide sequencing PCR-amplified gene products. Mutations considered be only if they found an independent tumor-derived PCR product but not matched normal tissue. Sequencing 9MB tumor sequence identified 239 putative genetic variants. further examined 22 variants RAS family 135 localized exons encoding kinase domain respective proteins. 37 non-synonymous mutations; 36 collectively KRAS, PIK3CA. One mutation was previously unreported (exon 16) FGFR4 (Glu681Lys), 1 158 tumors. is analogous reported tumor-specific ERBB2 located same exon as (Pro712Thr) adenocarcinoma line. Conclusions/Significance This study one first comprehensive analyses major specific sizeable adenocarcinomas. Our results suggest majority gain-of-function within have already been identified. findings also implicate pathogenesis subset