Analysis of significantly mutated genes as a clinical tool for the diagnosis in a case of lung cancer

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Findings on mutations, associated with lung cancer, have led to advancements in mutation-based precision medicine. This study aimed to comprehensively and synthetically analyze mutations in lung cancer, based on the next generation sequencing data of surgically removed lung tumors, and identify the mutation-related factors that can affect clinical outcomes. Targeted sequencing was performed on formalin-fixed paraffin-embedded surgical specimens obtained from 172 patients with lung cancer who underwent surgery in our hospital. The clinical and genomic databases of the hospital were combined to determine correlations between clinical factors and mutation profiles in lung cancer. Multivariate analyses of mutation-related factors that may affect the prognosis were also performed. Based on histology, TP53 was the driver gene in 70.0% of the cases of squamous cell carcinoma. In adenocarcinoma cases, driver mutations were detected in TP53 (26.0%), KRAS (25.0%), and epidermal growth factor receptor (EGFR) (23.1%). According to multivariate analysis, the number of pathogenic mutations (≥3), presence of a TP53 mutation, and TP53 allele fraction >60 were poor prognostic mutational factors. The TP53 allele fraction tended to be high in caudally and dorsally located tumors. Moreover, TP53-mutated lung cancers located in segments 9 and 10 were associated with significantly poorer prognosis than those located in segments 1–8. This study has identified mutation-related factors that affect the postoperative prognosis of lung cancer. To our knowledge, this is the first study to demonstrate that the TP53 mutation profile varies with the site of lung tumor, and that postoperative prognosis varies accordingly.

Section: Discussionmentioning

confidence: 99%

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

Goto

Kunimasa

Hirotsu

et al. 2020

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“…The pipeline included signal processing, base calling, quality score assignment, read alignment to the human genome 19 reference (hg19), quality control of mapping, and coverage analysis. Following data analysis, annotation of single nucleotide variants, insertions and deletions was performed using an Ion Reporter Server System (Thermo Fisher Scientific), and lymphocyte DNA from peripheral blood was used as a control to detect variants (tumor–normal pair analysis), as described previously [39,43,44].…”

Section: Methodsmentioning

confidence: 99%

Clinical Implications of Noncoding Indels in the Surfactant-Encoding Genes in Lung Cancer

Nakagomi

Hirotsu

Goto

et al. 2019

Lung cancer arises from the accumulation of genetic mutations, usually in exons. A recent study identified indel mutations in the noncoding region of surfactant-encoding genes in lung adenocarcinoma cases. In this study, we recruited 94 patients with 113 lung cancers (88 adenocarcinomas, 16 squamous cell carcinomas, and nine other histologies) who had undergone surgery in our department. A cancer panel was designed in-house for analyzing the noncoding regions, and targeted sequencing was performed. Indels in the noncoding region of surfactant-encoding genes were identified in 29/113 (25.7%) cases and represent the precise cell of origin for the lung cancer, irrespective of histological type and/or disease stage. In clinical practice, these indels may be used as clonal markers in patients with multiple cancers and to determine the origin of cancer of unknown primary site.

“…Additionally, EGFR mutations were detected from DNA obtained from EVs in bronchoalveolar lavage fluid (BALF) of non-small-cell lung cancer (NSCLC) patients [ 34 ]. However, the current drawbacks of using BALF or plasma are that BALF shows higher detection rate but is relatively invasive and thus not a routine procedure of bronchoscopy [ 35 ], while plasma is less invasive but shows lower detection rate compared to BALF [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Detection of EGFR Mutations Using Bronchial Washing-Derived Extracellular Vesicles in Patients with Non-Small-Cell Lung Carcinoma

Park

Lee

Eom

et al. 2020

The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.