CTDdgv: a comprehensive database for the identification and clinical interpretation of ctDNA driver genes and variants in cancer

Circulating tumor DNA (ctDNA) variants hold significant promise as cancer biomarkers in liquid biopsies, owing to their minimally invasive testing approach and capacity to capture the comprehensive tumor landscape. However, a comprehensive resource for studying ctDNA variants is still lacking. Here, we developed CTDdgv, which aims to identify ctDNA variants and interpret their clinical relevance systematically. We manually curated 1674 experimentally validated clinical interpretations for ctDNA variants, concerning prognostic significance, drug resistance, associations with tumor characteristics, metastasis monitoring, therapy guiding, prospect for detection, and others. Furthermore, we developed and integrated a pipeline that identifies tumor driver genes (TDGs) and variants (TDVs) and evaluates the prognostic significance of potential TDGs. Using publicly available ctDNA mutation spectra, we identified potential TDGs and TDVs from 38 datasets across 17 cancer types. Based on these data sets, we provide the multi-dimensional analysis of TDG gene sets in specific cancer types, providing insights into their driving effects. Collectively, CTDdgv has significant potential to serve as a valuable resource for molecular diagnostics and therapeutic decision-making in cancer via liquid biopsy.

循环肿瘤DNA（circulating tumor DNA, ctDNA）变异作为液体活检领域的癌症生物标志物具有巨大应用前景，因其检测方式微创性强，且能够全面反映肿瘤整体特征。然而，目前仍缺乏用于研究ctDNA变异的综合性数据库资源。本研究开发了CTDdgv数据库，旨在系统性识别ctDNA变异并阐释其临床相关性。我们人工注释整理了1674条经实验验证的ctDNA变异临床解读信息，涵盖预后意义、耐药性、与肿瘤特征的关联、转移监测、治疗指导、检测应用前景等多个维度。此外，我们开发并整合了一套分析流程，可识别肿瘤驱动基因（tumor driver genes, TDGs）及其变异（tumor driver variants, TDVs），并评估潜在肿瘤驱动基因的预后价值。基于公开可用的ctDNA突变谱数据，我们从覆盖17种癌症类型的38个数据集中共识别出潜在的TDGs与TDVs。基于上述数据集，我们针对特定癌症类型的TDG基因集开展了多维度分析，为其驱动肿瘤发生的作用机制提供了深入见解。综上，CTDdgv具备成为通过液体活检开展癌症分子诊断与治疗决策的重要数据库资源的巨大潜力。

搜集汇总

背景与挑战

背景概述

CTDdgv是一个全面的癌症ctDNA驱动基因和变异体数据库，包含1674个临床验证的变异体解释，并提供了识别驱动基因和变异体的分析流程。数据集覆盖17种癌症类型，包含基因、突变、预测和原始数据四个文件，旨在为癌症液体活检提供分子诊断和治疗决策支持。