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The utilization of next-generation sequencing to detect somatic mutations and predict clinical prognosis of Chinese non-small cell lung cancer patients.

ABSTRACT: Purpose:The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods:We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients. The sequences were analyzed for oncogenic mutations, which were then correlated to clinical prognosis and smoking history. Results:NGS of tumor biopsies detected both well-known driver mutations as well as rare or novel mutations. EGFR was the most frequently mutated gene, accounting for 32.4% (33/102) of the somatic mutations in this study. The EGFR mutations detected included rare variants such as EGFR exon 19 insertion (K745_E746insIPVAIK) and in cis H835L+L833V. Additionally, novel RET fusion mutations PCM1-RET and ADD3-RET were detected in two adenocarcinoma patients. To demonstrate the functional applications of NGS, we correlated mutations with patient characteristics, outcomes of matched targeted therapy, and outcomes based on allelic frequency of the EGFR-T790M mutation. Finally, we demonstrated that circulating tumor DNA can be used both to measure response to targeted therapy and as a predictor of clinical outcome, by presenting a case study of a single patient. Conclusion:We demonstrated that NGS can be used in multiple applications to effectively identify potential oncogenic driver mutations, guide mutation-targeted therapy decisions, and predict clinical outcomes in Chinese NSCLC patients.

SUBMITTER: Cao L

PROVIDER: S-EPMC5951221 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The utilization of next-generation sequencing to detect somatic mutations and predict clinical prognosis of Chinese non-small cell lung cancer patients.

Cao Liming L Long Long L Li Min M Yang Huaping H Deng Pengbo P Mao Xinru X Xiang Jianxing J Li Bing B Zhang Tengfei T Hu Chengping C

OncoTargets and therapy 20180508

<h4>Purpose</h4>The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients.<h4>Materials and methods</h4>We perf ...[more]

PMID: 29780256

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Project description:IntroductionMultiple primary melanomas (MPM) occur up to 8% of patients with cutaneous malignant melanoma (CMM). They are often sporadic harbouring several somatic mutations, but also familial cases harbouring a CDKN2A germline mutation have been describe in Caucasian populations. The aim of this study was to investigate the incidence, the distribution patterns and the impact of known and unknown germline and somatic mutations in patients with MPM from Italy.Materials and methodsOne-hundred and two MPM patients were enrolled for germline mutation analysis, and five patients with at least four MPMs were identified for somatic mutation analysis. The demographic, pathologic and clinical features were retrieved from medical records. Molecular analysis for both germline and somatic mutations was performed in genomic DNA from peripheral blood and tissue samples, respectively, through a next generation sequencing approach, using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup for somatic analysis and a commercial cancer hotspot panel for somatic analysis.ResultsCDKN2A mutations were detected in 6/16 (37.5%) and 3/86 (3.5%) MPM cases with and without family history for melanoma, respectively. Furthermore, multiple MC1R and, to a lesser extent, ATM variants have been identified. BAP1 variants were found only in MPM patients from southern Italy. The most frequent somatic variants were the pathogenic BRAFV600E and TP53, followed by KIT, PIK3CA, KDR, and NRAS. Single APC, ERBB4, MET, JAK3 and other variants with unknown function were also detected.ConclusionsCDNK2A mutation is the most relevant susceptibility mutation in Italian patients with MPM, especially those with a family history for CMM. The prevalence of this mutation and other sequence variants identified in this study varies among specific sub-populations. Furthermore, some heterogeneity in driver somatic mutations between sporadic MPMs has been observed, as well as in a number of associated sequence variants the clinical impact of which needs to be further elucidated.

Dataset Information

The utilization of next-generation sequencing to detect somatic mutations and predict clinical prognosis of Chinese non-small cell lung cancer patients.

Publications

The utilization of next-generation sequencing to detect somatic mutations and predict clinical prognosis of Chinese non-small cell lung cancer patients.

Similar Datasets

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