文章：

超越基因融合：靶向RNA测序面板在复杂基因内结构重排中的临床应用扩展

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements

原文发布日期：2 September 2023

DOI: 10.3390/cancers15174394

类型: Article

开放获取: 是

英文摘要：

Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to include intragenic rearrangements, such as internal tandem duplications (ITDs) or exon-level deletions. These intragenic events have been increasingly implicated as cancer-promoting events. However, the detection of intragenic rearrangements may be challenging to resolve bioinformatically with short-read sequencing technologies and therefore may not be routinely assessed in panel-based testing. Within an academic clinical laboratory, over three years, a total of 608 disease-involved samples (522 hematologic malignancy, 86 solid tumors) underwent clinical testing using Anchored Multiplex PCR (AMP)-based RNA sequencing. Hematologic malignancies were evaluated using a custom Pan-Heme 154 gene panel, while solid tumors were assessed using a custom Pan-Solid 115 gene panel. Gene fusions, ITDs, and intragenic deletions were assessed for diagnostic, prognostic, or therapeutic significance. When considering gene fusions alone, we report an overall diagnostic yield of 36% (37% hematologic malignancy, 41% solid tumors). When including intragenic structural rearrangements, the overall diagnostic yield increased to 48% (48% hematologic malignancy, 45% solid tumor). We demonstrate the clinical utility of reporting structural rearrangements, including gene fusions and intragenic structural rearrangements, using an AMP-based RNA sequencing panel.

摘要翻译： 

基因融合是一种结构重排形式，已被确认为儿童和成人癌症的驱动事件。识别此类事件对于癌症的精准分型、预后评估及治疗方案制定具有临床意义。结构重排不仅限于基因融合，还包括基因内重排，例如内部串联重复（ITDs）或外显子水平缺失。这些基因内事件作为促癌因素的作用日益受到关注。然而，利用短读长测序技术进行生物信息学解析时，基因内重排的检测可能面临挑战，因此在基于基因组合的检测中可能未被常规评估。 在一家学术临床实验室为期三年的研究中，共有608份疾病相关样本（522份血液系统恶性肿瘤，86份实体瘤）采用基于锚定多重PCR（AMP）的RNA测序进行临床检测。血液系统恶性肿瘤使用定制的泛血液154基因组合进行评估，实体瘤则使用定制的泛实体瘤115基因组合进行分析。研究评估了基因融合、ITDs和基因内缺失在诊断、预后或治疗方面的意义。 仅考虑基因融合时，我们报告的总体诊断检出率为36%（血液系统恶性肿瘤37%，实体瘤41%）。当纳入基因内结构重排时，总体诊断检出率提升至48%（血液系统恶性肿瘤48%，实体瘤45%）。本研究通过基于AMP的RNA测序组合，证明了报告结构重排（包括基因融合和基因内结构重排）的临床实用性。

原文链接：

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements