Pathologist-initiated whole genome and transcriptome sequencing demonstrates diagnostic utility in resolving difficult-to-diagnose tumors.

IF 10.4 1区生物学 Q1 GENETICS & HEREDITY

Genome Medicine Pub Date : 2025-10-07 DOI:10.1186/s13073-025-01534-5

Joseph H A Vissers, Catherine Mitchell, Owen W J Prall, Wing-Yee Lo, Sehrish Kanwal, Stephen J Luen, Stephen C Watts, Christopher M Angel, Christine Khoo, Jia-Min B Pang, William K Murray, Cameron Snell, Michael Christie, Richard J Rebello, Richard W Tothill, Kym Pham, Oliver Hofmann, Stephen B Fox, Sean M Grimmond

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引用次数: 0

Abstract

Background: Despite significant advances in diagnostic cancer histopathology, a subset of tumors are unable to be classified using WHO criteria. The resulting diagnostic uncertainty can result in inappropriate clinical management and negative patient outcomes.

Methods: We investigated whether combining histopathology with whole genome and transcriptome sequencing (WGTS) could improve the classification of tumors that posed diagnostic dilemmas despite extensive histopathology and standard molecular work-up at a quaternary oncology center.

Results: We successfully sequenced 45 tumors from an initial set of 54 unclassified tumors (83% success rate). A confident diagnosis was made for 35/45 tumors (78%). Additionally, potential treatment targets were identified in 21/45 tumors (47%). Theoretical comparison with alternative assays demonstrated that WGTS was uniquely capable of detecting critical diagnostic findings in 9/35 tumors (26%).

Conclusions: This work supports augmenting histopathology and standard molecular pathology with WGTS in the classification of difficult-to-diagnose tumors.

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病理学家发起的全基因组和转录组测序在解决难以诊断的肿瘤方面显示了诊断效用。

背景：尽管在诊断癌症组织病理学方面取得了重大进展，但仍有一部分肿瘤无法使用WHO标准进行分类。由此产生的诊断不确定性可能导致不适当的临床管理和患者的负面结果。方法：我们研究了将组织病理学与全基因组和转录组测序（WGTS）相结合是否可以改善肿瘤的分类，尽管在第四纪肿瘤中心进行了广泛的组织病理学和标准的分子检查，但仍存在诊断困境。结果：我们从54个未分类的肿瘤中成功测序了45个肿瘤（成功率83%）。对35/45个肿瘤（78%）做出了可靠的诊断。此外，在21/45的肿瘤（47%）中确定了潜在的治疗靶点。与其他检测方法的理论比较表明，WGTS在9/35的肿瘤（26%）中具有独特的检测关键诊断结果的能力。结论：本研究支持WGTS对难以诊断肿瘤的组织病理学和标准分子病理学的增强。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genome Medicine GENETICS & HEREDITY-

CiteScore

20.80

自引率

0.80%

发文量

128

审稿时长

6-12 weeks

期刊介绍： Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.