【佳学基因靶向药物基因检测】绘制与肝内胆管癌中可操作驱动因素相关的共突变模式

千万不要做检测基因合理吗

挖掘基因组组学个性化药物选择记录《J Hepatol》在 2022 Dec 15;S0168-8278(22)03328-1.发表了一篇题目为《Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Gajanan Kendre, Karthikeyan Murugesan, Tilman Brummer, Oreste Segatto, Anna Saborowski, Arndt Vogel等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。 这项研究对肿瘤诊断和治疗有以下几点重要意义: 通过分析大样本数据集,深入洞察了胆管细胞性肝内胆管癌(iCCA)的分子亚组特点和基因组异质性,有助于这种罕见癌症的精准诊疗。 该研究对iCCA中7种重要致癌驱动基因的共突变谱进行了详细分析,这对开发相关的靶向治疗策略具有指导意义。 发现负选择规律的存在,如RTK/RAS/ERK通路的共突变,为临床用药提供了依据。 识别了一些特定亚组如MSI高和TMB高的特征突变,可作为这些肿瘤的生物标志物。 这项研究结果可为iCCA相关的临床试验设计、动物模型建立、耐药机制研究等提供参考,推动iCCA精准医疗的发展。 强调了进行肿瘤分子检测的必要性,指导个体化的靶向治疗策略。 提供了一个可参考的iCCA基因组数据库,有利于这类罕见癌症研究的开展。 总体来说,这项研究丰富了iCCA的基因组特征数据,有助于发展诊断标志物和精准治疗策略,对改善这种肿瘤的临床结果具有积极意义。

肿瘤基因检测及靶向药物治疗研究关键词：

胆道癌,基因组改变,免疫疗法,精准医疗,靶向治疗。

肿瘤治疗检测基因临床应用结果

背景与目的：近年来，肝内胆管癌 (iCCA) 已发展成为胃肠道癌症精准肿瘤学的“榜样”。然而，它的稀有性及其基因组异质性对靶向治疗的发展和演变提出了挑战。询问大型数据集有助于更好地了解罕见癌症分子亚组的特征，并能够识别在较小队列中仍未被识别的基因组模式。佳学基因解码的途径：我们对 FoundationCORE 数据库中诊断为 iCCA 的 6,130 名接受诊断面板的患者进行了回顾性分析FoundationOne 平台上的测序。评估了超过 300 个肿瘤相关基因的短变异/融合重排和拷贝数改变，并且大多数队列的肿瘤突变负荷 (TMB) 以及微卫星不稳定性 (MSI) 状态可用。靶向药物研究的客观数据：我们提供 iCCA 基因组景观的高度代表性制图，并概述七个治疗相关的致癌驱动基因的共突变谱：IDH1/2、FGFR2、ERBB2、BRAF、MDM2、BRCA1/2、MET 和 KRASG12C。我们观察到 RTK/RAS/ERK 通路共同改变的负选择，以及 IDH1/2 和 FGFR2 改变患者中表观遗传修饰因子（如 ARID1A 和 BAP1）的富集。 RNF43 以及 KMT2D 在 MSIhigh 和 TMBhigh 肿瘤中以高频率发生。药物指导及病因判断的依据：对最普遍的基因组星座的详细了解是制定 iCCA 有效治疗策略的关键。我们的研究提供了宝贵的资源，可用于评估临床试验和亚组分析的可行性，促进转化相关临床前模型的发展，并作为知识库来预测基因组定义的亚组中靶向治疗的潜在耐药机制。影响和意义：由于可靶向改变的频率很高，建议对胆道癌患者进行分子诊断，尤其是 iCCA 患者。然而，可操作病变的识别并不能保证治疗成功，并且共突变谱可能作为药物反应的关键调节剂。使用来自 6,130 名 iCCA 患者的综合面板测序结果的大型数据集，我们提供了最常见的药物基因改变的共突变谱的详细分析，旨在作为建立遗传相关临床前模型的参考，开发假设驱动的联合疗法并确定复发性遗传特征。关键词：胆道癌；基因组改变；免疫疗法；精准医疗；靶向治疗。

肿瘤发生与革命国际数据库描述：

Background & aims: In recent years, intrahepatic cholangiocarcinoma (iCCA) has evolved as a "role model" for precision oncology in gastrointestinal cancers. However, its rarity, paired with its genomic heterogeneity, challenges the development and evolution of targeted therapies. Interrogating large datasets drives better understanding of the characteristics of molecular subgroups of rare cancers and enables the identification of genomic patterns that remain unrecognized in smaller cohorts.Methods: We performed a retrospective analysis of 6,130 patients diagnosed with iCCA from the FoundationCORE database who received diagnostic panel sequencing on the FoundationOne platform. Short variants/fusion-rearrangements and copy number alterations in >300 tumor-associated genes were evaluated, and the tumor mutational burden (TMB) as well as the microsatellite instability (MSI) status were available for the majority of the cohort.Results: We provide a highly representative cartography of the genomic landscape of iCCA and outline the co-mutational spectra of seven therapeutically relevant oncogenic driver genes: IDH1/2, FGFR2, ERBB2, BRAF, MDM2, BRCA1/2, MET and KRASG12C. We observed a negative selection of RTK/RAS/ERK pathway co-alterations, and an enrichment of epigenetic modifiers such as ARID1A and BAP1 in patients with IDH1/2 and FGFR2 alterations. RNF43 as well as KMT2D occurred with high frequency in MSIhigh and TMBhigh tumors.Conclusion: Detailed knowledge of the most prevalent genomic constellations is key to the development of effective treatment strategies for iCCA. Our study provides a valuable resource that could be used to assess the feasibility of clinical trials and subgroup analyses, spurs the development of translationally relevant preclinical models, and serves as a knowledge base to predict potential mechanisms of resistance to targeted therapies in genomically defined subgroups.Impact and implications: Due to the high frequency of targetable alterations, molecular diagnostics is recommended in patients with biliary tract cancers, and especially in those with iCCA. The identification of an actionable lesion, however, does not guarantee therapeutic success, and the co-mutational spectrum may act as a critical modifier of drug response. Using a large dataset of comprehensive panel sequencing results from 6,130 patients with iCCA, we provide a detailed analysis of the co-mutational spectrum of the most frequent druggable genetic alterations, which is meant to serve as a reference to establish genetically relevant preclinical models, develop hypothesis-driven combination therapies and identify recurrent genetic profiles.Keywords: biliary tract cancer; genomic alterations; immunotherapy; precision medicine; targeted therapy.