Bødker Julie S, Sønderkær Mads, Vesteghem Charles, Schmitz Alexander, Brøndum Rasmus F, Sommer Mia, Rytter Anne S, Nielsen Marlene M, Madsen Jakob, Jensen Paw, Pedersen Inge S, Grubach Lykke, Severinsen Marianne T, Roug Anne S, El-Galaly Tarec C, Dybkær Karen, Bøgsted Martin
Department of Haematology, Clinical Cancer Research Centre, Aalborg University Hospital, Sdr. Skovvej 15, DK-9000 Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, DK-9000 Aalborg, Denmark.
Cancers (Basel). 2020 Jan 29;12(2):312. doi: 10.3390/cancers12020312.
Within recent years, many precision cancer medicine initiatives have been developed. Most of these have focused on solid cancers, while the potential of precision medicine for patients with hematological malignancies, especially in the relapse situation, are less elucidated. Here, we present a demographic unbiased and observational prospective study at Aalborg University Hospital Denmark, referral site for 10% of the Danish population. We developed a hematological precision medicine workflow based on sequencing analysis of whole exome tumor DNA and RNA. All steps involved are outlined in detail, illustrating how the developed workflow can provide relevant molecular information to multidisciplinary teams. A group of 174 hematological patients with progressive disease or relapse was included in a non-interventional and population-based study, of which 92 patient samples were sequenced. Based on analysis of small nucleotide variants, copy number variants, and fusion transcripts, we found variants with potential and strong clinical relevance in 62% and 9.5% of the patients, respectively. The most frequently mutated genes in individual disease entities were in concordance with previous studies. We did not find tumor mutational burden or micro satellite instability to be informative in our hematologic patient cohort.
近年来，已经开展了许多精准癌症医学计划。其中大多数都集中在实体癌上，而精准医学对血液系统恶性肿瘤患者的潜力，尤其是在复发情况下，尚未得到充分阐明。在此，我们在丹麦奥尔堡大学医院开展了一项无人口统计学偏差的观察性前瞻性研究，该医院是丹麦10%人口的转诊中心。我们基于全外显子组肿瘤DNA和RNA的测序分析，开发了一种血液学精准医学工作流程。详细概述了所涉及的所有步骤，说明了所开发的工作流程如何为多学科团队提供相关分子信息。一组174例患有进展性疾病或复发的血液学患者被纳入一项非干预性的基于人群的研究，其中92例患者样本进行了测序。基于对小核苷酸变异、拷贝数变异和融合转录本的分析，我们分别在62%和9.5%的患者中发现了具有潜在和强烈临床相关性的变异。各个疾病实体中最常发生突变的基因与先前的研究一致。我们没有发现肿瘤突变负荷或微卫星不稳定性在我们的血液学患者队列中具有参考价值。
