ArticleMolecular oncology2018
Subjecting appropriate lung adenocarcinoma samples to next-generation sequencing-based molecular testing: challenges and possible solutions.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Case Report: Two cases of non-small cell lung cancer with coexistence ofFrontiers in oncology · 2025Article
- Liquid-based cytology specimens for next-generation sequencing in lung adenocarcinoma: challenges and evaluation of targeted therapy.BMC cancer · 2024Article
- [Cytology Smears of Rapid On-site Evaluation as Supplemental Material for Molecular Testing of Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
- Investigating genomic, proteomic, and post-transcriptional regulation profiles in colorectal cancer: a comparative study between primary tumors and associated metastases.Cancer cell international · 2023Article
- Developing an effective quality evaluation strategy of next-generation sequencing for accurate detecting non-small cell lung cancer samples with variable characteristics: a real-world clinical practice.Journal of cancer research and clinical oncology · 2023Article
- Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC.Frontiers of medicine · 2023Article
- Genomic and Glycolytic Entropy Are Reliable Radiogenomic Heterogeneity Biomarkers for Non-Small Cell Lung Cancer.International journal of molecular sciences · 2023Article
- Reliability analysis of exonic-breakpoint fusions identified by DNA sequencing for predicting the efficacy of targeted therapy in non-small cell lung cancer.BMC medicine · 2022Article
- Genetic and immune characteristics of multiple primary lung cancers and lung metastases.Thoracic cancer · 2021Article
- [Analysis of the Relationship Between the Quality of Small Biopsy Specimens of Non-small Cell Lung Cancer and the Mutation Rate of EGFR Gene].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- Metastatic NSCLCs With Limited Tissues: How to Effectively Identify Driver Alterations to Guide Targeted Therapy in Chinese Patients.JTO clinical and research reports · 2021Article
- The Role of Whole Exome Sequencing in Distinguishing Primary and Secondary Lung Cancers.Lung Cancer (Auckland, N.Z.) · 2021Review
- Next Generation Sequencing in Non-Small Cell Lung Cancer: Pitfalls and Opportunities.Diagnostics (Basel, Switzerland) · 2020Review
- Genetic features and application value of next generation sequencing in the diagnosis of synchronous multifocal lung adenocarcinoma.Oncology letters · 2020Article
- Value of pre-therapyEuropean journal of nuclear medicine and molecular imaging · 2020Article
- PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.Cancers · 2019Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting appropriate tissue samples to NGS testing were explored. The results showed that lower frequencies of HER2/BRAF/PIK3CA and acquired EGFR T790M mutations were observed in biopsy samples with <20% tumor cellularity than in those with ≥20%, but there were no significant differences in the frequencies of EGFR or KRAS mutations. Moreover, tumor heterogeneity was assessed by heterogeneity score (HS), which was calculated through multiplying by 2 the mutant allele frequency (MAF) of tumor cells. In TKI-naive samples, intratumor heterogeneity could occur in EGFR, KRAS, HER2, BRAF, and PIK3CA mutant tumors, but the degree was variable. Higher EGFR, but lower BRAF and PIK3CA HS values were observed compared with KRAS HS. In TKI-relapsed samples, analysis of concomitant sensitizing EGFR and T790M MAFs showed that intratumor heterogeneity was common in acquired EGFR T790M mutant tumors. The mutational status between primary and metastatic tumors was usually concordant, but KRAS, HER2, and PIK3CA HS were significantly higher in metastatic tumors than in primary tumors. Additionally, the discordance rate of mutational status in multifocal lung adenocarcinomas diagnosed as equivocal or multiple primary tumors was high. Together, our findings demonstrate that a comprehensive quality assessment is necessary during tissue process to mitigate the challenges of poor tumor cellularity, tumor heterogeneity, and multifocal clonally independent tumors.
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