title: Genetic alteration profiling of patients with resected squamous cell lung carcinomas.
abstract: In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC.
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Tao
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor
keywords: fluorescence in situ hybridization; genetic alteration; next-generation sequencing; squamous cell lung carcinoma; targeted therapy