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

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, prognost...

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Bibliographic Details
Published in:	Experimental and molecular pathology Vol. 139; p. 104920
Main Authors:	Racu, Marie-Lucie, Schiavo, Andrea Alex, Van Campenhout, Claude, De Nève, Nancy, Masuy, Thomas, Maris, Calliope, Decaestecker, Christine, Remmelink, Myriam, Salmon, Isabelle, D'Haene, Nicky
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Inc 01-10-2024 Elsevier
Subjects:	Adult Aged Aged, 80 and over Biomarkers, Tumor - genetics Carcinoma, Pancreatic Ductal - diagnosis Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - pathology Chromosome 18 loss of heterozygosity (LOH) Copy number alteration (CNA) DNA Copy Number Variations - genetics Female High-Throughput Nucleotide Sequencing - methods Humans Loss of Heterozygosity - genetics Male Middle Aged Mutation - genetics Next-generation sequencing (NGS) Pancreatic ductal adenocarcinoma (PDAC) Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Prognosis Smad4 Protein - genetics Chromosome 18 loss of heterozygosity (LOH) Copy number alteration (CNA) Pancreatic ductal adenocarcinoma (PDAC) Next-generation sequencing (NGS)
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Summary:	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. •PDAC molecular profiling is used for diagnostic, prognostic and theranostic purposes.•Targeted NGS (tNGS) is an effective approach in daily practice for TAT and cost.•This study focuses on the validation of a tNGS panel integrating evaluation of LOH status.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0014-4800 1096-0945 1096-0945
DOI:	10.1016/j.yexmp.2024.104920