利用非编码区保证基于小样本组的肿瘤突变负荷估计的准确性。

IF 5.7 2区 医学 Q1 Medicine
Cancer Science Pub Date : 2024-10-01 DOI:10.1111/cas.16342
Takahiro Nishino, Mio Yumura, Kuniko Sunami, Takashi Kubo, Hitoshi Ichikawa, Tomoyo Yasuda, Eisaku Furukawa, Momoko Nagai, Yasushi Yatabe, Mamoru Kato, Takashi Kohno
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引用次数: 0

摘要

要准确估算肿瘤突变负荷(TMB),并将其作为免疫检查点抑制剂反应性的预测指标,需要足够的基因组规模。目前对 TMB 的计算只考虑编码区,而大多数基因面板检测都会询问非编码区。利用非编码区是解决面板规模限制的一个潜在解决方案。然而,纳入非编码区对 TMB 估计准确性的影响仍不清楚。本研究使用 OncoGuide NCC Oncopanel System (NOP) 调查了利用非编码区补充面板规模的有效性。本研究的目的是评估正交检测的测试性能,与免疫检查点抑制剂反应性的关联不在评估范围内。我们使用全外显子测序(WES)和FoundationOne®CDx(F1CDx)检测法比较了仅从编码区(NOP-编码)和从编码区及非编码区(NOP-overall)计算的TMB状态和数值。我们的研究结果表明,在 WES(OPA:96.7% vs. 73.3%,n = 30)和 F1CDx(OPA:90.0% vs. 73.3%)中,与 NOP 编码相比,NOP-overall 显著提高了与 TMB 状态的总体一致性百分比(OPA)。此外,与 WES 相比,NOP-整体(3.55 [95% CI: 0.98-6.13])的 TMB 值平均差异低于 NOP 编码(6.22 [95% CI: 3.73-8.70])。这些结果体现了纳入非编码区以保持小规模面板中准确的 TMB 估计值的实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Leveraging non-coding regions to guarantee the accuracy of small-sized panel-based tumor mutational burden estimates.

Accurate estimation of tumor mutational burden (TMB) as a predictor of responsiveness to immune checkpoint inhibitors in gene panel assays requires an adequate panel size. The current calculations of TMB only consider coding regions, while most of gene panel assays interrogate non-coding regions. Leveraging the non-coding regions is a potential solution to address this panel size limitation. However, the impact of including non-coding regions on the accuracy of TMB estimates remains unclear. This study investigated the validity of leveraging non-coding regions to supplement panel size using the OncoGuide NCC Oncopanel System (NOP). The aim of this study was to evaluate test performance against orthogonal assays and the association with responsiveness to immune checkpoint inhibitors was not included in the evaluation. We compared TMB status and values between TMB calculated only from coding regions (NOP-coding) and from both coding and non-coding regions (NOP-overall) using whole exome sequencing (WES) and FoundationOne®CDx (F1CDx) assay. Our findings revealed that NOP-overall significantly improved the overall percent agreement (OPA) with TMB status compared with NOP-coding for both WES (OPA: 96.7% vs. 73.3%, n = 30) and F1CDx (OPA: 90.0% vs. 73.3%). Additionally, the mean difference in TMB values compared with WES was lower for NOP-overall (3.55 [95% CI: 0.98-6.13]) than for NOP-coding (6.22 [95% CI: 3.73-8.70]). These results exemplify the utility of incorporating non-coding regions to maintain accurate TMB estimates in small-sized panels.

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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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