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.
摘要：
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，我们旨在验证用于临床常规的靶向下一代测序（tNGS）小组，研究对PDAC诊断重要的基因，预后和潜在的热无关方面。在该NGS面板中，我们还设计了目标区域来询问18号染色体的杂合性（LOH）丢失，这可能与更严重的疾病进展有关。也已经探索了基因子集的拷贝数改变。最后两种方法通常不用于tNGS面板的常规诊断，我们研究了它们对更好地表征PDAC的可能贡献。使用该组表征来自140名患者的一系列140个福尔马林固定石蜡包埋(FFPE)PDAC样品。92%的患者在至少一个被研究的基因中显示出改变(最常见的KRAS，TP53、SMAD4、CDKN2A和RNF43)。关于LOH评估，我们能够从20%细胞肿瘤百分比开始检测到chr18LOH。chr18上LOH的存在与更差的无疾病和无转移生存率有关，在单变量和多变量分析中。本研究验证了使用tNGS面板进行PDAC表征，还评估chr18LOH状态以进行预后分层。
