Abstract
We investigated the frequency of major driver oncogenes in lung adenosquamous cell carcinoma (ASC) cases. Frequency of EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA gene mutations was examined in 56 patients using next-generation sequencing, polymerase chain reaction, and Sanger sequencing. Macrodissection or microdissection was performed in 37 cases to separate the adenomatous and squamous components of ASC. The overall mutation rate was 64.29%, including 55.36%, 7.14%, and 1.79% for EGFR, K-Ras, and B-Raf mutations, respectively. PIK3CA mutation was detected in three cases; all involved coexisting EGFR mutations. Of the 37 cases, 34 were convergent in two components, while three showed EGFR mutations in the glandular components and three showed PIK3CA mutations in the squamous components. With respect to EGFR mutations, the number of young female patients, nonsmokers, and those with positive pleural invasion was higher in the mutation-positive group than that in the mutation-negative. K-Ras mutation was significantly associated with smoking. Overall survival in the different EGFR mutation groups differed significantly. The frequency and clinicopathological characteristics of EGFR- and K-Ras-mutated adenosquamous lung carcinoma were similar to that noted in Asian adenocarcinomas patients. The high convergence mutation rate in both adenomatous and squamous components suggests monoclonality in ASC.
Highlights
Driver oncogenes were reported to be potential targeted genes, they included B-Raf, Kirsten rat sarcoma viral oncogene homolog (K-Ras), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), discoidin domain receptor tyrosine kinase 2 (DDR2), and platelet-derived growth factor receptor alpha polypeptide (PDGFRA), et al The B-Raf is a proto-oncogene that is a serine/threonine kinase downstream from KRAS in the mitogen-activated protein kinase (MAPK) signalling cascade and can be targeted by Vemurafenib or GSK2118436
Adenosquamous carcinoma (ASC) is a rare variant of non-small cell lung cancer (NSCLC), with a poorer prognosis relative to those of the other types of NSCLC9
Few studies have evaluated the frequency of major driver oncogene mutations in ASC, with most focusing on epidermal growth factor receptor (EGFR) gene mutation[10,11]
Summary
Driver oncogenes were reported to be potential targeted genes, they included B-Raf, Kirsten rat sarcoma viral oncogene homolog (K-Ras), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), discoidin domain receptor tyrosine kinase 2 (DDR2), and platelet-derived growth factor receptor alpha polypeptide (PDGFRA), et al The B-Raf is a proto-oncogene that is a serine/threonine kinase downstream from KRAS in the mitogen-activated protein kinase (MAPK) signalling cascade and can be targeted by Vemurafenib or GSK2118436. K-Ras can initiate cell proliferation through the RAS-dependent kinase cascade and is associated with a worse overall survival (OS) in patients with NSCLC8. PIK3CA is a family of lipid kinases that plays an important role in regulating cell growth, proliferation, and survival. Several reports have been published regarding epidermal growth factor receptor (EGFR) mutation in patients with ASC of the lung but there are few studies concerning other genetic changes in ASC. We used polymerase chain reaction (PCR), next-generation (NGS), and Sanger sequencing methods, focusing on the hotspots of seven driver oncogenes, including EGFR, K-Ras, B-Raf, PIK3CA, DDR2, ALK, and PDGFRA, to identify major genetic alterations in patients with ASC of the lung. Our study focused mainly on genetic alternations and the implications for origination issues
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