Dataset Information

Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features.

ABSTRACT:

Background

Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations.

Objectives

We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarkers observed in other types of lung cancer.

Methods

We screened formalin-fixed paraffin-embedded (FFPE) biopsy tissues of 32 Chinese SCLC patients using the 303 oncogenic driver gene panel generated by Tiling PCR amplification sequencing (tPAS) and analyzed the patients' corresponding serum protein levels of CYFRA21-1 CEA, NSE, and SCCA.

Results

In total, we found 147 SCLC-related mutant genes, among these, three important genes (TP53, RB1, KMT2D) as well as five novel genes LRRK2, BRCA1, PTCH1, ARID2, and APC that altogether occurred in 90% of patients. Furthermore, increased mutations to 6 genes (WT1, NOTCH1, EPHA3, KDM6A, SETD2, ACVR1B) significantly associated with higher serum NSE levels (P = 0.0016) and higher clinical stages II + III compared to stage I (P = 0.06).

Conclusions

Our panel is relatively reliable in detecting the oncogenic mutations of Chinese SCLC patients. Based on our findings, it may be possible to combine SCLC-related mutations and serum NSE for a simple detection of clinical staging.

SUBMITTER: Jin W

PROVIDER: S-EPMC8046547 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features.

Jin Wang W Lei Zhao Z Xu Sun S Fachen Zhou Z Yixiang Zhang Z Shilei Zhao Z Tao Guo G Zhe Sun S Fengzhou Li L Su Wen-Hui WH Chundong Gu G

BioMed research international 20210405

<h4>Background</h4>Small cell lung cancer (SCLC) is an aggressive and invasive malignancy that presents at advanced clinical stage with no more effective treatments. Development of a method for its early detection would be useful, also new therapeutic target need to be discovered; however, there is a lack of information about its oncogenic driver gene mutations.<h4>Objectives</h4>We aim to identify the SCLC-related genomic variants that associate with clinical staging and serum protein biomarker ...[more]

PMID: 33880365

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Project description:Background: Recent advanced technologies, such as high-throughput sequencing, have enabled the identification of a broad spectrum of variants. Using targeted-gene-panel resequencing for Parkinson's disease (PD)-associated genes, we have occasionally found several single-nucleotide variants (SNVs), which are thought to be disease-associated, in PD patients. To confirm the significance of these potentially disease-associated variants, we performed genome association analyses, using next-generation target resequencing, to evaluate the associations between the identified SNVs and PD. Methods: We obtained genomic DNA from 766 patients, who were clinically diagnosed with PD, and 336 healthy controls, all of Japanese origin. All data were analyzed using Ion AmpliSeq panel sequences, with 29 PD- or dementia-associated genes in a single panel. We excluded any variants that did not comply with the Hardy-Weinberg equilibrium in the control group. Variant frequencies in the PD and control groups were compared using PLINK. The identified variants were confirmed to a frequency difference of P < 0.05, after applying the Benjamini-Hochberg procedure using Fisher's exact test. The pathogenicity and prevalence of each variant were estimated based on a public gene database. Results: We identified three rare variants that were significantly associated with PD: rs201012663/rs150500694 in SYNJ1 and rs372754391 in DJ-1, which are intronic variants, and rs7412 in ApoE, which is an exonic variant. The variants in SYNJ1 and ApoE were frequently identified in the control group, and rs201012663/rs150500694 in SYNJ1 may play a protective role against PD. The DJ-1 variant was frequently identified in the PD group, with a high odds ratio of 2.2. Conclusion: The detected variants may represent genetic modifiers or disease-related variants in PD. Targeted-gene-panel resequencing may represent a useful method for detecting disease-causing variants and genetic association studies in PD.

Dataset Information

Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features.

Background

Objectives

Methods

Results

Conclusions

Publications

Genetic Mutation Analysis in Small Cell Lung Cancer by a Novel NGS-Based Targeted Resequencing Gene Panel and Relation with Clinical Features.

Similar Datasets

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