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舌部和喉部头颈部鳞状细胞癌细胞系的高分辨率拷贝数和基因表达微阵列分析。

High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx.

作者信息

Järvinen Anna-Kaarina, Autio Reija, Kilpinen Sami, Saarela Matti, Leivo Ilmo, Grénman Reidar, Mäkitie Antti A, Monni Outi

机构信息

Institute of Biomedicine and Biomedicum Biochip Center, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.

出版信息

Genes Chromosomes Cancer. 2008 Jun;47(6):500-9. doi: 10.1002/gcc.20551.

Abstract

Gene amplifications and deletions are frequent in head and neck squamous cell carcinomas (SCC) but the association of these alterations with gene expression is mostly unknown. Here, we characterized genome-wide copy number and gene expression changes on microarrays for 18 oral tongue SCC (OTSCC) cell lines. We identified a number of altered regions including nine high-level amplifications such as 6q12-q14 (CD109, MYO6), 9p24 (JAK2, CD274, SLC1A1, RLN1), 11p12-p13 (TRAF6, COMMD9, TRIM44, FJX1, CD44, PDHX, APIP), 11q13 (FADD, PPFIA1, CTTN), and 14q24 (ABCD4, HBLD1, LTBP2, ZNF410, COQ6, ACYP1, JDP2) where 9% to 64% of genes showed overexpression. Across the whole genome, 26% of the amplified genes had associated overexpression in OTSCC. Furthermore, our data implicated that OTSCC cell lines harbored similar genomic alterations as laryngeal SCC cell lines We have previously analyzed, suggesting that despite differences in clinicopathological features there are no marked differences in molecular genetic alterations of these two HNSCC sites. To identify genes whose expression was associated with copy number increase in head and neck SCC, a statistical analysis for oral tongue and laryngeal SCC cell line data were performed. We pinpointed 1,192 genes that had a statistically significant association between copy number and gene expression. These results suggest that genomic alterations with associated gene expression changes play an important role in the malignant behavior of head and neck SCC. The identified genes provide a basis for further functional validation and may lead to the identification of novel candidates for targeted therapies. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

摘要

基因扩增和缺失在头颈部鳞状细胞癌(SCC)中很常见,但这些改变与基因表达之间的关联大多未知。在此,我们对18个口腔舌鳞状细胞癌(OTSCC)细胞系的全基因组拷贝数和基因表达变化进行了微阵列特征分析。我们鉴定出了一些改变区域,包括9个高水平扩增区域,如6q12 - q14(CD109、MYO6)、9p24(JAK2、CD274、SLC1A1、RLN1)、11p12 - p13(TRAF6、COMMD9、TRIM44、FJX1、CD44、PDHX、APIP)、11q13(FADD、PPFIA1、CTTN)以及14q24(ABCD4、HBLD1、LTBP2、ZNF410、COQ6、ACYP1、JDP2),其中9%至64%的基因表现出过表达。在整个基因组中,26%的扩增基因在OTSCC中存在相关的过表达。此外,我们的数据表明OTSCC细胞系具有与我们之前分析的喉鳞状细胞癌细胞系相似的基因组改变,这表明尽管临床病理特征存在差异,但这两个头颈部鳞状细胞癌部位的分子遗传改变并无明显差异。为了鉴定其表达与头颈部鳞状细胞癌拷贝数增加相关的基因,我们对口腔舌和喉鳞状细胞癌细胞系数据进行了统计分析。我们确定了1192个在拷贝数和基因表达之间存在统计学显著关联的基因。这些结果表明,伴有相关基因表达变化的基因组改变在头颈部鳞状细胞癌的恶性行为中起重要作用。所鉴定的基因提供了进一步功能验证之基础,并可能有助于鉴定靶向治疗的新候选物。本文包含可在http://www.interscience.wiley.com/jpages/1045 - 2257/suppmat获取的补充材料。

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