Low-frequency of RABL3 pathogenetic variants in hereditary and familial pancreatic cancer

Puzzono, Marta; Crippa, Stefano; Zuppardo, Raffaella Alessia; Zapparoli, Ettore; Falconi, Massimo; Cavestro, Giulia Martina

doi:10.1016/j.dld.2020.11.024

Cited by 2 publications

(1 citation statement)

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“…While this variant was observed at a frequency of 0.19% in our dataset, this was not statistically significantly higher than the frequency observed in non‐cancer cases in gnomAD (Table 2; 0.13%, P = .36). Our findings are in agreement with a recently published report that did not identify the p.S36X and p.R194Q variants in 66 patients with pancreatic cancer 26 …”

Section: Discussionsupporting

confidence: 94%

Germline sequence analysis of RABL3 in a large series of pancreatic ductal adenocarcinoma patients reveals no evidence of deleterious variants

Roberts

Grant

Gallinger

et al. 2021

Genes Chromosomes & Cancer

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5‐year survival rate of less than 10%. Individuals with a pathogenic germline variant in a pancreatic cancer susceptibility gene are at an increased risk of developing pancreatic cancer. Understanding the inherited genetic basis of pancreatic tumor development provides a unique opportunity to improve patient care and outcomes. For example, relatives of a patients with PDAC who have a pathogenic germline variant in a pancreatic cancer susceptibility gene are eligible for disease surveillance where cancers may be detected early, and 5‐year survival greatly improved. Furthermore, for some patients with PDAC and a pathogenic germline variant in a pancreatic cancer susceptibility gene, their tumors may be susceptible to specific anti‐cancer therapies. Recently, RABL3 was identified as a pancreatic cancer susceptibility gene. To validate these findings and inform clinical translation, we determined the prevalence of deleterious RABL3 variants in a large cohort of 1037 patients with PDAC that had undergone either whole genome or whole exome germline sequencing. We identified two synonymous variants and four missense variants classified as variants of unknown significance. We found no pathogenic RABL3 variants, indicating that the maximum prevalence of such variants in patients with PDAC is less than 0.36% (minor allele frequency 0, 97.5% one‐sided confidence interval: 0‐0.0036). This finding has important implications for germline genetic testing of patients with PDAC.

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Section: Discussionsupporting

confidence: 94%