Whole-exome sequencing as a tool for searching for genetic background modifiers in MEN1 patients with neuroendocrine pancreatic tumours, including insulinomas

Abstract

family and is unpredictable based on available data [3][4][5]. MEN1 is a dominantly inherited, monogenic disorder that develops in patients with pathogenic variants in the MEN1 gene. All carriers of pathogenic variants in this gene will develop MEN1 syndrome throughout their lives. Tissue specificity of the tumour suppressor role of MEN1 has been proven, which explains the general picture of the disease with the classical P-triad being a hallmark of the disease [1]. However, correlations between types of variants and clinical outcomes seem to exist only in a very limited manner. For most of the variants, no such correlations have been found despite multiple analyses that have been performed on this issue [6][7][8]. An association between large rearrangements in MEN1 and earlier onset of MEN1 syndrome has been identified [9], and in some

Whole-Exome Screening and Analysis of Signaling Pathways in Multiple Endocrine Neoplasia Type 1 Patients with Different Outcomes: Insights into Cellular Mechanisms and Possible Functional Implications

“…Fifteen symptomatic patients with genetically confirmed MEN1 were invited to participate in the study, including members from 4 families. In total, 10 of the patients, including 6 members from 2 families, were classified for downstream analyses based on their clinical characteristics, the remainder were included in different analyses (published elsewhere, [12]). The pathogenicity of the germline MEN1 variants was verified based on their deleterious impact on the gene structure (frameshift and nonsense variants, large deletions) and available databases (Varsome [31], NCBI ClinVar [32], LOVD [33]).…”

“…Gene ontology and pathway analyses were conducted to identify overrepresented biological processes in patients with a given disease outcome. We have recently published results for the pancreatic aspect of the disease (including insulinoma) [12]. Here, we analyze the state of pituitary tumors and adrenocortical tumors in the course of MEN1.…”