Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?

6533b852fe1ef96bd12aac7e

RESEARCH PRODUCT

Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?

Christian Rolfo Jean Charles Dagorn Ezequiel Calvo Giuseppe Bronte Santini Daniele Daniele Fanale Juan L. Iovanna Antonio Russo Viviana Bazan Patrice Berthezene Giuseppe Cicero Pascal Belleau

subject

Male copy number variations germline alteration pancreatic cancer susceptibility YTHDC2 gene DNA Copy Number Variations Settore MED/06 - Oncologia Medica Clinical Biochemistry Adenocarcinoma Biology Germline Pancreatic cancer Drug Discovery medicine Humans Genetic Predisposition to Disease Multiplex Prospective Studies Multiplex ligation-dependent probe amplification Copy-number variation Allele Gene Germ-Line Mutation Aged Adenosine Triphosphatases Aged 80 and over Pharmacology Pharmacology. Therapy DNA Helicases Middle Aged medicine.disease Molecular biology Pancreatic Neoplasms Case-Control Studies Molecular Medicine Adenocarcinoma Female Multiplex Polymerase Chain Reaction RNA Helicases

description

Abstract: Objective: The vast majority of pancreatic cancers occurs sporadically. The discovery of frequent variations in germline gene copy number can significantly influence the expression levels of genes that predispose to pancreatic adenocarcinoma. We prospectively investigated whether patients with sporadic pancreatic adenocarcinoma share specific gene copy number variations (CNVs) in their germline DNA. Patients and methods: DNA samples were analyzed from peripheral leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma and from 60 controls using Affymetrix 500K array set. Multiplex ligation-dependent probe amplification (MLPA) assay was performed using a set of self-designed MLPA probes specific for seven target sequences. Results: We identified a CNV-containing DNA region associated with pancreatic cancer risk. This region shows a deletion of 1 allele in 36 of the 72 analyzed patients but in none of the controls. This region is of particular interest since it contains the YTHDC2 gene encoding for a putative DNA/RNA helicase, such protein being frequently involved in cancer susceptibility. Interestingly, 82.6% of Sicilian patients showed germline loss of one allele. Conclusions: Our results suggest that the YTHDC2 gene could be a potential candidate for pancreatic cancer susceptibility and a useful marker for early detection as well as for the development of possible new therapeutic strategies.

year	journal	country	edition	language
2014-01-01	Expert Opinion on Therapeutic Targets

https://doi.org/10.1517/14728222.2014.920324