Genome-Scale Analysis Identifies Novel Transcript-Variants in Esophageal Adenocarcinoma

A study published in Cellular and Molecular Gastroenterology and Hepatology (Purkayastha, 2020, Cell Mol Gastroenterol Hepatol) used genome-scale analysis to identify novel gene isoforms, or transcript-variants, in esophageal adenocarcinoma (EAC). Identification of these transcript variants may be used to develop future biomarkers and/or therapeutic targets to fight this increasingly prevalent and aggressive esophageal malignancy.

Portrait of Kishore Guda, DVM, PhD
Kishore Guda, DVM, PhD

Gene isoforms are alternative RNA and/or protein signals produced from the same gene, explained study lead Kishore Guda, DVM, PhD, associate professor of oncology and pathology at the Case Western Reserve University School of Medicine and member of the Case Comprehensive Cancer Center. To date, the prevalence and significance of such alternative transcript isoforms in EAC remains unknown. This study represents the first genome-wide analysis identifying novel transcript-variants induced in EAC, and a step toward better understanding their role in tumor formation.

Through RNA sequencing of tumor biopsies obtained from treatment-naïve esophageal cancer patients followed by computational analysis, the team identified novel transcript-variants of genes induced in EACs. Of these, a novel transcript-variant of the Collagen X alpha 1 chain precursor gene, termed COL10A1Var1, was prioritized for further studies based on the pathway's known link to other cancers. Further studies identified COL10A1Var1 as a recurrent EAC-associated transcript-variant with a potential tumor-promoting function. Specifically, the team found COL10A1Var1 to be robustly induced in the majority of EACs (~60%), and also found evidence of COL10A1 isoforms as potential regulators of EAC tumor cell migration and mechanosensing ability.

The study is led by Kishore Guda, DVM, PhD. Additional team members include Biswa Pratim Das Purkayastha, E. Ricky Chan, PhD, Durgadevi Ravillah, Lakshmeswari Ravi, Rajesh Gupta, Joseph E. Willis, MD, Amitabh Chak, MD, Vinay Varadan, PhD from Case Western Reserve University; Marcia I. Canto, MD from Johns Hopkins University; Jean S. Wang, MD, PhD from Washington University; Nicholas J. Shaheen, MD, MPH from University of North Carolina Chapel Hill.

This work was supported by National Institutes of Health grants: R01CA204549, U01CA152756, U54CA163060, P50CA150964, K25DK115904, P30CA043703, K24DK100548, P30DK034987, P30 DK89502, and by The DeGregorio Family Foundation, The Savone Family and the Esophageal Cancer Awareness Association.