title: Screening for major driver oncogene alterations in adenosquamous lung carcinoma using PCR coupled with next-generation and Sanger sequencing methods.
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.
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Department of Pathology, Beijing 100730, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Shi
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Department of Pathology, Beijing 100730, China.
authors.forename: Huanwen
authors.initials: H
authors.lastname: Wu
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Department of Pathology, Beijing 100730, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Department of Pathology, Beijing 100730, China.
authors.forename: Huanli
authors.initials: H
authors.lastname: Duan
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Department of Pathology, Beijing 100730, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Department of Pathology, Beijing 100730, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D011905:Genes, ras; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D066246:ErbB Receptors