PO.CL01.10 · 临床研究
组织和液体活检样本的高通量基因组分析揭示了印度人群NSCLC患者中的可靶向突变
High throughput genomic profiling of tissue and liquid biopsy samples reveals targetable mutations in NSCLC patients from the Indian population
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：非小细胞肺癌（NSCLC）约占肺癌病例的85%，是全球癌症相关死亡的首要原因，它既高度侵袭性，又以拥有最广泛的已批准靶向治疗谱为独特特征。使用二代测序（NGS）进行的综合基因组分析（CGP）已成为临床实践中不可或缺的部分，其中基于组织和血浆的游离循环肿瘤DNA（ctDNA）分析是NSCLC中最成熟且应用最广泛的方式。为解决印度NSCLC患者分子数据匮乏的问题，本研究旨在通过对FFPE和血浆ctDNA样本进行基于NGS的分析来描绘突变谱，推动靶向治疗和精准医学的进步。
方法：本研究纳入了来自NSCLC患者的45份FFPE组织和血浆标本，从而能够对实体活检和液体活检方法进行稳健的比较。使用G2M PanCan CGP检测方法对总共45份样本进行综合基因组分析，该方法靶向681个临床相关基因，约1.7 Mb的基因组区域，并在Illumina平台上进行测序。使用GATK v4.1.2体细胞变异检出流程进行生物信息学分析，并使用MAF tools实现突变全景和热点区域的下游可视化。
结果：在FFPE组织和血浆ctDNA样本中均检测到一致的突变，其中TP53的显著改变频率最高且临床相关性最强，同时伴有EGFR、ASXL1和ARID1A的改变。在FFPE中变异等位基因频率为6-39%，在液体活检样本中为0.9-3.0%，该检测方法在不同样本类型中均证明有效，产生了高度一致的突变谱。TP53是最常突变的基因，表现出G325、P152L、H179D和L194R等热点变异，凸显了其在NSCLC发病机制中的关键作用。
结论：通过绘制关键NSCLC相关基因中的突变，本研究证实基于NGS的综合基因组分析在FFPE组织和血浆ctDNA样本中提供了可靠且一致的检测。这一发现凸显了该检测方法在将组织和液体活检整合到常规临床实践中的效用，为临床医生提供准确的基因组见解，以指导靶向突变驱动的治疗决策。
查看英文原文 English abstract
Background: Non-Small Cell Lung Cancer (NSCLC), accounts for approximately 85% of lung cancer cases and ranking as the foremost cause of cancer related deaths globally, is both highly aggressive and uniquely characterized by the broadest spectrum of approved targeted treatments. Comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) has become integral to clinical practice, with tissue and plasma-based analysis of cell free circulating tumor DNA (ctDNA) representing the most established and widely adopted modality in NSCLC. Addressing the scarcity of molecular data in Indian NSCLC patients, this study aims to delineate the mutational spectrum through NGS based profiling of FFPE and plasma ctDNA samples, driving advances in targeted therapy and precision medicine.
Methods: The study included 45 FFPE tissue and plasma specimens from NSCLC patients, enabling a robust comparison of solid and liquid biopsy approaches. Comprehensive genomic profiling was performed on a total of 45 samples using the G2M PanCan CGP assay, which targets 681 clinically relevant genes with approximately 1.7 Mb of genomic regions and was sequenced on the Illumina platform. Bioinformatics analysis was conducted using the GATK v4.1.2 somatic variant calling pipeline, and downstream visualization of mutational landscapes and hotspot regions was achieved using MAF tools.
Results: Consistent mutations were detected in both FFPE tissue and plasma ctDNA samples, with prominent alterations in TP53 showing the highest frequency and clinical relevance, accompanied by alterations in EGFR, ASXL1 and ARID1A. With variant allele frequencies of 6-39% in FFPE and 0.9-3.0% in liquid biopsy samples, the assay proved effective across sample types, producing a highly concordant mutational profile. TP53 was the most frequently mutated gene, exhibiting hotspot variants such as G325, P152L, H179D, and L194R, underscoring its critical role in NSCLC pathogenesis.
Conclusions: By mapping mutations in key NSCLC associated genes, the investigation confirms that NGS-based comprehensive genomic profiling delivers reliable and concordant detection across FFPE tissue and plasma ctDNA samples. This finding highlights the assay's utility for integrating tissue and liquid biopsy into routine clinical practice, empowering clinicians with accurate genomic insights to guide targeted mutation driven therapy decisions.
利益披露 Disclosure
A. Kumar, None..
P. Sinha, None..
R. Chandran, None..
S. Gupta, None..
G. Tessarin, None.