Association of Mutation Profiles with Postoperative Survival in Patients with Non–Small Cell Lung Cancer

Goto, Taichiro; Kunimasa, Kei; Hirotsu, Yosuke; Nakagomi, Takahiro; Yokoyama, Yujiro; Higuchi, Rumi; Otake, Sotaro; Oyama, Toshio; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

doi:10.3390/cancers12113472

Cited by 8 publications

(4 citation statements)

References 49 publications

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“…In line with previous studies [ 49 , 50 ], the changes in mutational burden were also observed during the disease progression in our study. Guo and colleagues reported decreasing VAF percentages (10% or more) for EGFR alterations in several patient samples after surgical treatment [ 51 ].…”

Section: Discussionsupporting

confidence: 93%

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

Sestokaite

Gedvilaite

Cicėnas

et al. 2023

IJMS

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Non-small cell cancer (NSCLC) has been identified with a great variation of mutations that can be surveyed during disease progression. The aim of the study was to identify and monitor lung cancer-specific mutations incidence in cell-free DNA as well as overall plasma cell-free DNA load by means of targeted next-generation sequencing. Sequencing libraries were prepared from cell-free DNA (cfDNA) isolated from 72 plasma samples of 41 patients using the Oncomine Lung cfDNA panel covering hot spot regions of 11 genes. Sequencing was performed with the Ion Torrent™ Ion S5™ system. Four genes were detected with highest mutation incidence: KRAS (43.9% of all cases), followed by ALK (36.6%), TP53 (31.7%), and PIK3CA (29.3%). Seven patients had co-occurring KRAS + TP53 (6/41, 14.6%) or KRAS + PIK3CA (7/41, 17.1%) mutations. Moreover, the mutational status of TP53 as well an overall cell-free DNA load were confirmed to be predictors of poor progression-free survival (HR = 2.5 [0.8–7.7]; p = 0.029 and HR = 2.3 [0.9–5.5]; p = 0.029, respectively) in NSCLC patients. In addition, TP53 mutation status significantly predicts shorter overall survival (HR = 3.4 [1.2–9.7]; p < 0.001). We demonstrated that TP53 mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.

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Section: Discussionsupporting

confidence: 93%

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

Sestokaite

Gedvilaite

Cicėnas

et al. 2023

IJMS

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“…We have focused on 53 major genes that have been shown to be involved or implicated in lung cancer formation ( Supplementary Table S1 ), which are described in The Cancer Genome Atlas [ 15 , 16 ]. Targeted deep sequencing was performed as described previously [ 17 , 18 , 19 , 20 , 21 ]. Briefly, primer design and library construction were carried out using Ion AmpliSeq™ Designer and Library Kit 2.0, respectively (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer

Otake

Goto

Higuchi

et al. 2022

Cancers

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Although bronchoscopy is generally performed to diagnose lung cancer, its diagnostic yield remains unsatisfactory. Assuming that lung cancer cells release cell-free DNA into the epithelial lining fluid, we hypothesized that lung cancer could be diagnosed by analyzing gene mutations in cell-free DNA in this fluid. This study included 32 patients with lung cancer who underwent surgery at our hospital. Bronchoalveolar lavage (BAL) was performed on the resected lung samples (ex vivo BAL model) after lobectomy. Each DNA sample (i.e., BAL fluid, primary lesion, and plasma) underwent deep targeted sequencing. Gene mutation analyses in the BAL fluid samples identified mutations identical to those in the primary lesions in 30 (93.8%) of 32 patients. In contrast, the microscopic cytology of the same BAL fluid samples yielded a diagnosis of lung cancer in only one of 32 patients, and the analysis of plasma samples revealed gene mutations identical to those in the primary lesions in only one of 32 patients. In conclusion, cell-free DNA released from lung cancer cells exists more abundantly in the airway than in the blood. The collection and analysis of the BAL fluid containing cell-free DNA derived from lung cancer can thus allow lung cancer diagnosis and the screening of driver mutations.

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“…Next‐generation sequencing (NGS) can reveal the whole gene profile of patients with lung cancer 12‐15 . The Oncomine Dx Target Test Multi‐CDx system, which was approved by the Food and Drug Administration in June 2017 in the United States, was approved in Japan as a companion diagnostic test in June 2019.…”

Section: Introductionmentioning

confidence: 99%

Actionable driver DNA variants and fusion genes can be detected in archived cytological specimens with the Oncomine Dx Target Test Multi‐CDx system in lung cancer

Amemiya

Hirotsu

Nagakubo

et al. 2021

Cancer Cytopathology

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BACKGROUND Molecular testing is critical for identifying actionable variants in lung cancer for precision medicine. When tumor tissue samples are unavailable, archived cytological specimens (ACSs) can be used. The authors examined whether oncogenic variants could be accurately detected in ACSs versus paired formalin‐fixed, paraffin‐embedded (FFPE) tumor tissues with in vitro diagnostic tests. METHODS The authors collected 18 ACSs and 15 FFPE tissues from 15 patients with lung cancer and investigated genomic profiles with the Oncomine Dx Target Test Multi‐CDx system, which is an integrated next‐generation sequencing platform that comprehensively examines 4 companion diagnostic target genes (epidermal growth factor receptor [EGFR]; B‐Raf proto‐oncogene, serine/threonine kinase [BRAF]; anaplastic lymphoma kinase [ALK]; and ROS proto‐oncogene 1, receptor tyrosine kinase [ROS1]). They compared the quantity and quality of extracted nucleic acids, the sequencing quality control (QC), and the detected variants between ACSs and FFPE tissues. RESULTS The total amount of DNA and RNA obtained from 1 slide was higher in FFPE tissues than ACSs. The RNA integrity number was higher in ACSs. There were no differences in sequencing QC between ACSs and FFPE tissues. A total of 21 variants, including EGFR mutations and ALK and ROS1 fusion genes, were detected in both ACSs and FFPE tissues with 100% concordance. CONCLUSIONS ACSs can be a feasible alternative with which to identify actionable mutations and fusion genes via the Oncomine Dx Target Test Multi‐CDx system.

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Association of Mutation Profiles with Postoperative Survival in Patients with Non–Small Cell Lung Cancer

Cited by 8 publications

References 49 publications

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression

The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer

Actionable driver DNA variants and fusion genes can be detected in archived cytological specimens with the Oncomine Dx Target Test Multi‐CDx system in lung cancer

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