VSIG10L may be a susceptibility gene for familial syndrome of esophageal adenocarcinoma and Barrett esophagus, according to a study published in JAMA Oncology.1
Researchers performed whole exome sequencing from peripheral lymphocyte DNA on 4 distant relatives from a multiplex, multigenerational family. The goal was to identify novel disease susceptibility variants in a familial syndrome of esophageal adenocarcinoma and Barrett esophagus, which they termed Barrett esophagus, through the use of high-throughput sequencing.
Gene variants were filtered and verified, and segregation analysis was performed to identify a single candidate variant. Gene expression analysis was performed with both quantitative real-time polymerase chain reaction and in situ RNA hybridization.
They utilized a 3-dimensional organotypic cell culture model of esophageal maturation to determine the phenotypic effects of gene variants.
A germline mutation, S631G, was identified in a highly-conserved serine residue in the uncharacterized gene VSIG10L that was segregated in affected family members. Upon transfection of the S631G variant into a 3-dimensional organotypic culture model of normal esophageal squamous cells, it was found that epithelial maturation was dramatically inhibited compared to wild-type.
VSIG10L exhibited high expression in normal squamous esophagus with a marked loss of expression in Barrett-associated lesions.
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“Further research assessing VSIG10L function may reveal pathways important for esophageal maturation and the pathogenesis of Barrett esophagus and esophageal adenocarcinoma,” the authors concluded.
- Fecteau RE, Konh J, Kresak A, et al. Association between germline mutation in VSIG10L and familial Barrett neoplasia. JAMA Oncol. 28 Jul 2016. doi:10.1001/jamaoncol.2016.2054 [Epub ahead of print]