Rare discrepancies in a driver gene alteration within histologically heterogeneous primary lung cancers

摘要: Abstract Objectives Most lung adenocarcinomas consist of mixtures histological subtypes harboring different frequencies driver gene mutations. However, little is known about intratumoral heterogeneity(ITH) within histologically heterogeneous primary cancers. Investigating key genes in respective morphological pattern crucial to personalized treatment. Methods Morphologically areas the same surgically resected were extracted from tissues analyze status each growth pattern. Driver genes, epidermal factor receptor (EGFR), KRAS and EML4-ALK, assessed by assays with sensitivities. Results Seventy-nine consecutive eligible patients a (EGFR = 65; KRAS = 10; EML4-ALK = 4) enrolled. For EGFR mutations, ITH occurred 13.3% (8/60) direct sequencing (DS) 1.7% (1/60) amplification refractory mutation system (ARMS) (P = 0.016) among adenocarcinomas, but consistent five adeno-squamous cell carcinomas both methods. mutations detected 20% (2/10) DS, whereas (10/10) high resolution melting. No discrepancies EML4-ALK rearrangements existed according fluorescence situ hybridization. Conclusion Rare ITHs EGFR/KRAS/EML4-ALK alterations methods higher sensitivity. Discrepancies might be due abundance mutant tumor cells detection assays.