CD3D mutation a possible predisposing factor in primary breast cancer development following Esophageal Squamous Cell Carcinoma (ESCC)

Background: Segregation analyses of families’ encountered cancer suggest that highly penetrant, autosomal dominant genes may be responsible for a number of primary tumors. Whole exom sequencing (WES) is broadly used to identify new molecular biomarkers in cancer. We aimed to identify novel susceptibility variants for primary breast tumor in patient already affected Result: Totally there were 66806 variants detected in the proband, however only a novel CD3D mutation in exonic region with damaging consequences to the protein was present in the proband but not the sister with only ESCC. This mutation resulted in a serine to cysteine substitution in cytoplasmic topological domain of the protein that is involved in T-cell development and signal transduction. It demonstrated segregation through generations. Conclusion: Detection of CD3D novel heterozygote mutation in the proband and half of her children and absence of this variant in the proband’s sister and her children suggested that it may be an important genetic factor for new primary breast tumor in ESCC patient. with esophageal squamous cell carcinoma (ESCC) focusing on Notch signaling pathway. Methods: A family was genetically analyzed with 26 members with a proband affected with two primary tumors of ESCC and breast and a sister affected only with ESCC primary tumor. The proband was examined through WES to generate information about genetic variants. To demonstrate protein structure, bioinformatic softwares were utilized. False positive investigation in NIH s database and comparing data with healthy samples was performed to exclude polymorphic regions. Analyzing the segregation of candidate variant was done through ARMS-PCR.

کلیدواژه ها:

Whole Exome Sequencing ، Esophageal Squamous Cell Carcinoma ، Breast cancer ، Notch signaling pathway ، predisposing factor