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

被引：2

作者：

Racu, Marie-Lucie ^{[1
]}

Schiavo, Andrea Alex ^{[1
]}

Van Campenhout, Claude ^{[1
]}

De Neve, Nancy ^{[1
]}

Masuy, Thomas ^{[1
]}

Maris, Calliope ^{[1
]}

Decaestecker, Christine ^{[2
,3
]}

Remmelink, Myriam ^{[1
]}

Salmon, Isabelle ^{[1
]}

D'Haene, Nicky ^{[1
]}

机构：

[1] Univ Libre Bruxelles ULB, Hop Univ Bruxelles HUB, CUB Hop Erasme, Dept Pathol, Route Lennik808, B-1070 Brussels, Belgium

[2] Univ Libre Bruxelles ULB, Ctr Microscopy & Mol Imaging CMMI, Digital Image Anal Pathol DIAPath, Gosselies, Belgium

[3] Univ Libre Bruxelles ULB, Ecole Polytech Bruxelles, Lab Image Synth & Anal LISA, Brussels, Belgium

来源：

EXPERIMENTAL AND MOLECULAR PATHOLOGY | 2024年 / 139卷

关键词：

Pancreatic ductal adenocarcinoma (PDAC); Next-generation sequencing (NGS); Copy number alteration (CNA); Chromosome 18 loss of heterozygosity (LOH); CANCER; MANAGEMENT; SURVIVAL; DELETION; GENE;

D O I：

10.1016/j.yexmp.2024.104920

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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.

引用

页数：12

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