OncoTargets and Therapy (May 2022)

Genomic Alteration Spectrum of Non-Small Cell Lung Cancer Patients in East-China Characterized by Tumor Tissue DNA and Cell-Free DNA

  • Li J,
  • Chen S,
  • Xue H,
  • Wang H,
  • Huang T,
  • Xie H,
  • He J,
  • Ke C,
  • Yu Z,
  • Ni B

Journal volume & issue
Vol. Volume 15
pp. 571 – 584

Abstract

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Jie Li,1,* Siwen Chen,1,* Hui Xue,2,* Haoyi Wang,3,* Tianwei Huang,4 Hongya Xie,5 Jiang He,6 Cai Ke,3 Zhaonan Yu,3 Bin Ni4 1Department of General Medical Ward, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Oncology Medical Ward, Hanzhong Central Hospital, Hanzhong, People’s Republic of China; 3Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Thoracic Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 6Department of Thoracic Surgery, Suzhou Wuzhong People’s Hospital, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Ni, Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 17774015977, Email [email protected] Zhaonan Yu, Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China, Tel +86 15558078770, Email [email protected]: From an oncologic perspective, genetic detection is becoming a frontline clinical test, used to identify actionable alterations for targeted therapy, monitor molecular clonal tumor evolution, indicate disease progression and prognosis, and predict medication efficacy and resistance. From analysis of both tumor tissue and cell-free DNA from a large cohort of non-small cell lung cancer patients in East-China, we characterized the full spectrum of genomic alterations.Methods: The study comprised 3000 unpaired samples including 1351 tumor tissue DNA (tDNA) and 1649 cell-free circulating tumor DNA (cfDNA) samples, from which 67 cancer-related genes were sequenced and the genetic alteration profiles were depicted. Integrative molecular analyses identified the frequently mutated genes, uncovered co-occurring somatic alterations, described the distribution of hotspot variants, analyzed the frequency of variant alleles, and notably distinguished actionable, novel variants.Results: The most commonly affected genes were EGFR, TP53, KRAS, CDKN2A, and PIK3CA in both tDNA and cfDNA samples. EGFR and CTNNB1, PIK3CA and PTEN, ERBB2 and SMO were found to have frequent co-occurring alterations in tDNA samples, while EGFR and SMO, KRAS and PDGFRA, PIK3CA and KDR were in cfDNA samples. A large number of primary druggable variants were identified in tDNA samples, while numerous drug-resistance variants, rare actionable variants, and non-EGFR actionable variants were detected in cfDNA samples. Novel variants were enriched in KDR, KIT, TP53, ABL1, FGFR1 in tDNA samples while the majority of novel variants were distributed in PDGFRA, EGFR, KIT, ROS1, BRCA2 in cfDNA samples. Variant allele frequency in tDNA samples was significantly (P < 0.001) higher than that in cfDNA samples.Conclusion: The results revealed considerable differences in the alteration characteristics between the two kinds of specimens. To date, this study represents the largest real-world investigation of its kind, derived from the largest number of patients in East-China. It reinforced and expanded the mechanism of molecular analysis of neoplastic genetic profiles.Keywords: real world study, non-small cell lung cancer patients in East-China, tumor tissue DNA, cell-free circulating tumor DNA, next-generation-sequencing, genetic alteration

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