Key points are not available for this paper at this time.
Abstract Esophageal Cancer is a deadly disease with a tendency to be diagnosed at the later stages. Considered a rare disease, accounting for 1. 1% of all cancers, EC comprises 2. 6% of all cancer deaths. The survival rate for all stages is 21. 7%. However, the survival rate decreases to 5. 6 % for advanced-stage cancers. EC is more common in men and associated with older age and heavy alcohol and tobacco use. In the last 25 years, the death rate of EC has been decreasing slightly from 4. 3 to 3. 7. The death rates for lung, prostate, and colon cancers have decreased by half in the same time frame. Therefore, novel therapies and biomarkers are urgently needed to accelerate survival and reduce the death rates by at least half for patients with EC. We previously completed exome sequencing in a small sample size and observed that the mutations in the noncoding regions of the EC genome are highly affected. In this study, we perform exome sequencing in 110 paired esophageal tumors and normal tissues using an Agilent SSELXT HS Exon V8+UTR library enrichment kit. Twelve paired EC and normal tissues are sequenced using the PacBio Hifi system. In WES, we detected almost half of the noncoding region mutations in the 3UTR and 2kb downstream regions of the genome, significantly affecting 51 oncogenic or tumor suppressor genes. In addition, the involved genes are over-represented in critical signaling pathways and transcriptional regulation of pluripotent stem cells. The number of changes in the 5UTR and 2kb upstream are similar to the number of variations in the intronic regions. Apoptosis, stress response, and DNA double-strand break repair pathways are affected by 5UTR mutations. Mutations in the intronic regions frequently occurred in pro-tumorigenic immune regulation genes, such as IL-33 and IL-6, and oncogene-induced senescence. The combined effect of these genetic and coding region mutations on oncogenes, significant signaling pathways, cancer cell stemness, DNA damage repair pathways, and immune system regulation may significantly impact poor prognosis in EC patients. Further studies will verify the effectiveness of targeting these genes for developing candidate therapeutics. Citation Format: Hayriye Verda Erkizan, Robert Wadleigh. Role of noncoding genome architecture in esophageal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7358.
Erkizan et al. (Fri,) studied this question.