Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
Carcinogenesis. 2010 Feb;31(2):208-15. doi: 10.1093/carcin/bgp209. Epub 2009 Nov 19.
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.
癌症是一种遗传性疾病，其中蛋白质编码基因和非编码 RNA（ncRNA）的相互作用起着根本作用。近年来，已对各种癌症中的人类基因组的完整编码成分进行了测序，而与 ncRNA 相关的此类尝试仍不完整。我们通过桑格技术筛选慢性淋巴细胞白血病（CLL）或结直肠癌（CRC）患者的 148 个 microRNA（miRNA）和超保守区（UCR）基因座的基因组 DNA 中的序列变异，并进一步尝试阐明其中一些变异的功能后果。我们在散发性和家族性 CLL 病例中发现了 miRNA 的序列变异，在 CLL 和 CRC 中发现了 UCR 的突变，并且在某些情况下，检测到了这些变异的功能影响。此外，通过将我们的数据与 miRNA 序列变异的先前发表的数据进行整合，我们创建了人类癌症中 miRNA/超保守基因 DNA 序列变异的目录。这些发现表明，ncRNA 是种系和体细胞突变以及具有人类肿瘤发生功能意义的单核苷酸多态性的靶标。ncRNA 基因座中的序列变异很常见，有些具有功能和生物学意义。此类信息可用于进一步在全基因组范围内研究 ncRNA 遗传变异的频率及其功能意义，以及开发白血病和癌的新的诊断和预后标志物。
