Investigation on the Role of PALB2 Gene in CDH1-Negative Patients With Hereditary Diffuse Gastric Cancer.

Abstract

INTRODUCTION:Not all patients with hereditary diffuse gastric cancer (HDGC) are found to carry germline pathogenic variants in the associated gene CDH1, which translates into a challenging clinical management and poor cancer prevention. Thus, several studies have searched for other candidate genes, among which stands PALB2. Our work explores the implication of this known cancer gene in HDGC.METHODS:We searched for germline PALB2 variants by Sanger sequencing in a series of 58 patients with HDGC who tested negative for CDH1 alterations.RESULTS:No clearly pathogenic variants in PALB2 were found in these patients. Only 5 rare genetic variants were identified, 3 of which were classified as variants of uncertain significance.DISCUSSION:Despite the promising association between PALB2 and HDGC suggested by certain works in the literature, our findings do not support PALB2 as a high predisposition gene for HDGC. Larger studies are needed to define its role in this disease and therefore improve cancer prevention.