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. 2022 Apr 23;12(5):1058.
doi: 10.3390/diagnostics12051058.

Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel

Deborah Malvi  1 , Francesco Vasuri  1 , Thais Maloberti  2   3 , Viviana Sanza  3 , Antonio De Leo  2   3 , Adele Fornelli  4 , Michele Masetti  5 , Claudia Benini  5 , Raffaele Lombardi  5 , Maria Fortuna Offi  5 , Mariacristina Di Marco  6   7 , Matteo Ravaioli  8   9 , Sirio Fiorino  10 , Enrico Franceschi  11 , Alba A Brandes  11 , Elio Jovine  5 , Antonietta D'Errico  1 , Giovanni Tallini  2   3 , Dario de Biase  12
Affiliations

Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel

Deborah Malvi et al. Diagnostics (Basel). .

Abstract

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence compared with KRAS wild-type tumors. Intriguingly, KRAS wild-type cases had a better short-term prognosis despite the lymph node status. In conclusion, our work highlights that the combination of KRAS mutation with the age of the patient and the lymph node status may help in predicting the outcome in PDAC patients.

Keywords: KRAS; PDAC; TP53; mutations; next-generation sequencing; pancreatic cancer.

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Conflict of interest statement

D.d.B. has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim and Eli Lilly that are unrelated to the current work.

Figures

Figure 1
Figure 1
Number of mutations detected by multigene NGS panel. WT, wild type.
Figure 2
Figure 2
Median overall survival (OS) in patients with PDAC without KRAS/TP53 mutations (WT), with a mutation in KRAS or TP53, and with mutations in KRAS and TP53 (KRAS + TP53). Months are reported on the Y-axis.
Figure 3
Figure 3
Kaplan–Meier curve comparing (a) PDAC KRAS-WT vs. KRAS-mut (p = 0.151); (b) PDAC TP53-WT vs. TP53-mut (* p = 0.037); (c) PDAC KRAS & TP53-mut vs. “other” PDAC (** p = 0.023); (d) PDAC KRAS & TP53-mut vs. KRAS-mut or TP53-mut vs. KRAS-WT and TP53-WT (*** p = 0.016). mut: mutated; WT, wild type.
Figure 4
Figure 4
Kaplan–Meier curve of patients with PDAC harboring KRAS & TP53 mutations and N2 lymph-nodal status.
See this image and copyright information in PMC

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