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.

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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.


  1. 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]