Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.
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 microRNAs (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.
Wojcik
Sylwia E
SE
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
Rossi
Simona
S
Shimizu
Masayoshi
M
Nicoloso
Milena S
MS
Cimmino
Amelia
A
Alder
Hansjuerg
H
Herlea
Vlad
V
Rassenti
Laura Z
LZ
Rai
Kanti R
KR
Kipps
Thomas J
TJ
Keating
Michael J
MJ
Croce
Carlo M
CM
Calin
George A
GA
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D022661:RNA, Untranslated / Q000235:genetics*
D035683:MicroRNAs; D022661:RNA, Untranslated