IsomiRs and tRNA-derived fragments are associated with metastasis and patient survival in uveal melanoma.
Publication/Presentation Date
1-1-2020
Abstract
Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. With over 50% of patients developing metastatic disease, there is an unmet need for improved diagnostic and therapeutic options. Efforts to understand the molecular biology of the disease have revealed several markers that correlate with patient prognosis, including the copy number of chromosome 3, genetic alterations in the BAP1, EIF1AX and SF3B1 genes, and other transcriptional features. Here, we expand upon previous reports by comprehensively characterizing the short RNA-ome in 80 primary UVM tumor samples. In particular, we describe a previously unseen complex network involving numerous regulatory molecules that comprise microRNA (miRNAs), novel UVM-specific miRNA loci, miRNA isoforms (isomiRs), and tRNA-derived fragments (tRFs). Importantly, we show that the abundance profiles of isomiRs and tRFs associate with various molecular phenotypes, metastatic disease, and patient survival. Our findings suggest deep involvement of isomiRs and tRFs in the disease etiology of UVM. We posit that further study and characterization of these novel molecules will improve understanding of the mechanisms underlying UVM, and lead to the development of new diagnostic and therapeutic approaches.
Volume
33
Issue
1
First Page
52
Last Page
62
ISSN
1755-148X
Published In/Presented At
Londin, E., Magee, R., Shields, C. L., Lally, S. E., Sato, T., & Rigoutsos, I. (2020). IsomiRs and tRNA-derived fragments are associated with metastasis and patient survival in uveal melanoma. Pigment cell & melanoma research, 33(1), 52–62. https://doi.org/10.1111/pcmr.12810
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
31283110
Department(s)
Administration and Leadership
Document Type
Article