Validation of a targeted next-generation sequencing panel for pancreatic ductal adenocarcinomas

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-07-20 DOI:10.1016/j.yexmp.2024.104920

Marie-Lucie Racu , Andrea Alex Schiavo , Claude Van Campenhout , Nancy De Nève , Thomas Masuy , Calliope Maris , Christine Decaestecker , Myriam Remmelink , Isabelle Salmon , Nicky D'Haene

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is reported to be amongst the cancers with the lowest survival rate at 5 years. In the present study we aimed to validate a targeted next-generation sequencing (tNGS) panel to use in clinical routine, investigating genes important for PDAC diagnostic, prognostic and potential theragnostic aspect. In this NGS panel we also designed target regions to inquire about loss of heterozygosity (LOH) of chromosome 18 that has been described to be possibly linked to a worse disease progression. Copy number alteration has also been explored for a subset of genes. The last two methods are not commonly used for routine diagnostic with tNGS panels and we investigated their possible contribution to better characterize PDAC. A series of 140 formalin-fixed paraffin-embedded (FFPE) PDAC samples from 140 patients was characterized using this panel. Ninety-two % of patients showed alterations in at least one of the investigated genes (most frequent KRAS, TP53, SMAD4, CDKN2A and RNF43). Regarding LOH evaluation, we were able to detect chr18 LOH starting at 20% cell tumor percentage. The presence of LOH on chr18 is associated with a worse disease- and metastasis-free survival, in uni- and multivariate analyses. The present study validates the use of a tNGS panel for PDAC characterization, also evaluating chr18 LOH status for prognostic stratification.

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胰腺导管腺癌靶向新一代测序面板的验证

据报道，胰腺导管腺癌（PDAC）是5年生存率最低的癌症之一。在本研究中，我们旨在验证临床常规使用的靶向新一代测序（tNGS）面板，调查对 PDAC 诊断、预后和潜在治疗方面有重要意义的基因。在这个 NGS 小组中，我们还设计了目标区域，以调查 18 号染色体的杂合性缺失（LOH），据描述，这种缺失可能与疾病恶化有关。我们还对部分基因的拷贝数改变进行了研究。后两种方法并不常用于 tNGS 面板的常规诊断，我们研究了它们对更好地描述 PDAC 特征可能做出的贡献。我们使用该面板对来自 140 名患者的 140 份福尔马林固定石蜡包埋（FFPE）PDAC 样本进行了特征描述。92%的患者至少有一个受检基因发生了改变（最常见的是KRAS、TP53、SMAD4、CDKN2A和RNF43）。在 LOH 评估方面，我们能够从 20% 的细胞肿瘤比例开始检测 chr18 LOH。在单变量和多变量分析中，chr18上存在LOH与较差的无疾病和无转移生存率有关。本研究验证了在 PDAC 特征描述中使用 tNGS 面板的有效性，同时还评估了用于预后分层的 chr18 LOH 状态。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464