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遗传分析的进展:来自一个案例研究的见解以及对兽医肿瘤学应用中的下一代测序技术的综述。

Advancements in genetic analysis: Insights from a case study and review of next-generation sequencing techniques for veterinary oncology applications.

作者信息

Harris R Adam, Nolan Jillian, Ammons Dylan, Beeson Samantha, Thamm Douglas, Avery Anne

机构信息

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA.

Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, USA.

出版信息

Vet Clin Pathol. 2024 Oct 4. doi: 10.1111/vcp.13388.

Abstract

Acute myeloid leukemia (AML) poses significant challenges in veterinary medicine, with limited treatment options and poor survival rates. While substantial progress has been made in characterizing human AML, translating these advancements to veterinary practice has been hindered by limited molecular understanding and diagnostic tools. The case study presented illustrates the application of whole genome sequencing in diagnosing AML in a dog, showcasing its potential in veterinary oncology. Our approach facilitated comprehensive genomic analysis, identifying mutations in genes that may be associated with AML pathogenesis in dogs, such as KRAS, IKZF1, and RUNX1. However, without supportive evidence of its clinical utility (eg, association with response to treatment or prognosis), the information is limited to exploration. This article reviews the comparative features of canine AML with human AML and discusses strategies to shrink the knowledge gap between human and veterinary medicine with cost-effective next-generation sequencing (NGS) techniques. By utilizing these approaches, the unique and shared molecular features with human AML can be identified, aiding in molecular classification and therapeutic development for both species. Despite the promise of NGS, challenges exist in implementing it into routine veterinary diagnostics. Cost considerations, turnaround times, and the need for robust bioinformatics pipelines and quality control measures must be addressed. Most importantly, analytical and clinical validation processes are essential to ensure the reliability and clinical utility of NGS-based assays. Overall, integrating NGS technologies into veterinary oncology holds great potential for advancing our understanding of AML and improving disease stratification, in hopes of improving clinical outcomes.

摘要

急性髓系白血病(AML)在兽医学中构成了重大挑战,治疗选择有限且存活率低。虽然在人类AML的特征描述方面取得了重大进展,但由于分子理解和诊断工具有限,将这些进展转化为兽医实践受到了阻碍。所呈现的案例研究说明了全基因组测序在诊断犬类AML中的应用,展示了其在兽医肿瘤学中的潜力。我们的方法有助于进行全面的基因组分析,识别可能与犬类AML发病机制相关的基因中的突变,如KRAS、IKZF1和RUNX1。然而,由于缺乏其临床实用性的支持证据(例如,与治疗反应或预后的关联),这些信息仅限于探索。本文回顾了犬类AML与人类AML的比较特征,并讨论了利用具有成本效益的下一代测序(NGS)技术缩小人类医学与兽医学之间知识差距的策略。通过采用这些方法,可以识别与人类AML独特和共有的分子特征,有助于两个物种的分子分类和治疗开发。尽管NGS前景广阔,但将其应用于常规兽医诊断仍存在挑战。必须解决成本考虑、周转时间以及对强大的生物信息学管道和质量控制措施的需求。最重要的是,分析和临床验证过程对于确保基于NGS的检测的可靠性和临床实用性至关重要。总体而言,将NGS技术整合到兽医肿瘤学中对于增进我们对AML的理解和改善疾病分层具有巨大潜力,有望改善临床结果。

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