Mutational analysis of apoptotic genes in familial aggregation of hematological malignancies.

Summary Introduction Apoptosis deregulation have been associated to tumorigenesis process and was highlighted as a prominent hallmark of cancer. Several mutations have been reported in several forms of Blood cancer. However, it has never been investigated in familial aggregations of hematological malignancies. Methods In this study, we performed a mutational analysis by sequencing the entire coding regions in four key apoptotic genes FAS, FASLG, CASP8 and CASP10 in 92 independent families belonging to French and Tunisian populations and diagnosed with several forms of familial hematological malignancies. Results We report 15 genetic variations among which 7 were previously reported in several form of cancers and have a potential effect on gene expression. Particularly, the CASP8 variants p.Asp302His and p.Lys337Lys were detected in 15% and 10% of our group of patients respectively and were previously reported in association to breast cancer and to breast cancer susceptibility. Discussion In this study, we do not report the underlining deleterious mutations in familial hematological malignancies, but we describe some variants with potential risk of developing blood cancer. To gain further insights on the association between apoptosis pathway deregulation and familial hematological malignancies, more apoptotic genes should be investigated.