Characterization of genomic alterations and the significance of PI3K/mTOR pathway mutations and tumor mutational burden in non‑small cell lung cancer

Hu,Jing; Shang,Yanhong; Shi,Xiaoliang; Zhang,Shuirong; Shi,Junping; Yao,Ming; Wang,Aodi; Shou,Tao; Shi,Weiwei; Wang,Kai; Liu,Angen; Pan,Xiaojie; Wang,Yongjie

doi:10.3892/or.2020.7559

Characterization of genomic alterations and the significance of PI3K/mTOR pathway mutations and tumor mutational burden in non‑small cell lung cancer

Authors:
- Jing Hu
- Yanhong Shang
- Xiaoliang Shi
- Shuirong Zhang
- Junping Shi
- Ming Yao
- Aodi Wang
- Tao Shou
- Weiwei Shi
- Kai Wang
- Angen Liu
- Xiaojie Pan
- Yongjie Wang
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Affiliations: Department of Medical Oncology, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei 71000, P.R. China, Origimed Co., Ltd., Shanghai 201114, P.R. China, Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
Published online on: March 23, 2020 https://doi.org/10.3892/or.2020.7559
Pages: 2053-2061

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Abstract

Lung cancer is the most prevalent cancer worldwide and non‑small cell lung cancer (NSCLC) is the most common subtype and accounts for 75% of all lung cancer cases. Although programmed death‑1/programmed death‑ligand‑1 (PD‑1/PD‑L1) blockade has shown good results in the clinic, numerous NSCLC patients still fail to respond to this therapy. In the current study, formalin‑fixed, paraffin‑embedded tumor and matched blood samples from 1,984 Chinese NSCLS patients were collected for detection of genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations and gene rearrangements. The most common mutated genes were tumor protein p53 (55.70%; 1,105/1,984), epidermal growth factor receptor (52.47%; 1,041/1,184), KRAS proto‑oncogene GTPase (13.36%, 265/1084), cyclin dependent kinase inhibitor 2A (12.30%; 244/1,984), LDL receptor related protein 1B (11.09%; 220/1,984) and telomerase reverse transcriptase (10.58%; 210/1,984). Tumor mutational burden was calculated and results revealed that it was associated with PI3K/mTOR pathway gene mutations, and patient's gender, age, smoking status, and tumor stage. In addition, mutations of phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α or F‑box and WD repeat domain containing 7 were detected in 3 patients with NSCLC who were resistant to PD‑1 inhibitors nivolumab and pembrolizumab. Disease stabilization and tumor shrinkage were observed in these patients after mTOR inhibitor everolimus treatment. The current data showed that NSCLC with PI3K/mTOR mutations are sensitive to mTOR inhibitors.

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