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.

Hereditary Diffuse Gastric Cancer: Molecular Genetics, Biological Mechanisms and Current Therapeutic Approaches

“…Although there is only limited evidence that PALB2 pathogenic gene variants might be associated with an increased risk for GC in CDH1 -negative patients [ 50 ], IGCLC recommends considering PALB2 testing in the case of unexplained gastric cancer in some families, alongside other genes associated with an increased risk of gastric cancer (eg. ATM , BRCA2 , Lynch syndrome genes, APC and TP53 ) [ 8 ].…”