Medical Faculty of Mannheim, Institute for Clinical Chemistry, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Nucleic Acids Res. 2010 Jan;38(Database issue):D682-9. doi: 10.1093/nar/gkp839. Epub 2009 Oct 9.
About 15% of human colorectal cancers and, at varying degrees, other tumor entities as well as nearly all tumors related to Lynch syndrome are hallmarked by microsatellite instability (MSI) as a result of a defective mismatch repair system. The functional impact of resulting mutations depends on their genomic localization. Alterations within coding mononucleotide repeat tracts (MNRs) can lead to protein truncation and formation of neopeptides, whereas alterations within untranslated MNRs can alter transcription level or transcript stability. These mutations may provide selective advantage or disadvantage to affected cells. They may further concern the biology of microsatellite unstable cells, e.g. by generating immunogenic peptides induced by frameshifts mutations. The Selective Targets database (http://www.seltarbase.org) is a curated database of a growing number of public MNR mutation data in microsatellite unstable human tumors. Regression calculations for various MSI-H tumor entities indicating statistically deviant mutation frequencies predict TGFBR2, BAX, ACVR2A and others that are shown or highly suspected to be involved in MSI tumorigenesis. Many useful tools for further analyzing genomic DNA, derived wild-type and mutated cDNAs and peptides are integrated. A comprehensive database of all human coding, untranslated, non-coding RNA- and intronic MNRs (MNR_ensembl) is also included. Herewith, SelTarbase presents as a plenty instrument for MSI-carcinogenesis-related research, diagnostics and therapy.
大约 15%的人类结直肠癌,以及在不同程度上的其他肿瘤实体,以及几乎所有与林奇综合征相关的肿瘤,都是由于错配修复系统缺陷导致的微卫星不稳定 (MSI) 的标志。由此产生的突变的功能影响取决于它们的基因组定位。编码单核苷酸重复序列 (MNR) 内的改变可导致蛋白质截断和新肽的形成,而未翻译的 MNR 内的改变可改变转录水平或转录稳定性。这些突变可能为受影响的细胞提供选择优势或劣势。它们可能进一步涉及微卫星不稳定细胞的生物学,例如通过产生由移码突变引起的免疫原性肽。选择性靶标数据库 (http://www.seltarbase.org) 是一个经过精心整理的公共微卫星不稳定人类肿瘤中越来越多的 MNR 突变数据的数据库。回归计算各种 MSI-H 肿瘤实体表明,统计上异常的突变频率预测 TGFBR2、BAX、ACVR2A 等,这些都被证明或高度怀疑与 MSI 肿瘤发生有关。许多用于进一步分析基因组 DNA、衍生的野生型和突变型 cDNA 和肽的有用工具都已集成。所有人类编码、非翻译、非编码 RNA 和内含子 MNR(MNR_ensembl)的综合数据库也包括在内。因此,SelTarbase 是与 MSI 致癌相关的研究、诊断和治疗的大量工具。