Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer

Sylwia E. Wojcik, Simona Rossi, Masayoshi Shimizu, Milena S. Nicoloso, Amelia Cimmino, Hansjuerg Alder, Vlad Herlea, Laura Z. Rassenti, Kanti R. Rai, Thomas J. Kipps, Michael J. Keating, Carlo M. Croce, George A. Calin

Research output: Contribution to journalArticle

Abstract

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 micro-RNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations.We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

Original languageEnglish
Article numberbgp209
Pages (from-to)208-215
Number of pages8
JournalCarcinogenesis
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 2010

ASJC Scopus subject areas

  • Cancer Research

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  • Cite this

    Wojcik, S. E., Rossi, S., Shimizu, M., Nicoloso, M. S., Cimmino, A., Alder, H., Herlea, V., Rassenti, L. Z., Rai, K. R., Kipps, T. J., Keating, M. J., Croce, C. M., & Calin, G. A. (2010). Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer. Carcinogenesis, 31(2), 208-215. [bgp209]. https://doi.org/10.1093/carcin/bgp209