Welcome to the Vanderbilt-Ingram Cancer Center Microarray Core webpage, spotlighting the latest information regarding genomic technologies as they relate to VICC interests. Members of the VICC are urged to contact the VMSR to find out how microarray, genotyping, and RNAi technologies may enhance their research. Three VMSR bioinformaticists are available to help members design and plan experiments, obtain high-quality data, and prepare the data for publication. New platforms, products, and analysis techniques allow exploration of genomics in ways never before possible.
Featured research
Analysis of host- and tumor-derived proteinases using a custom dual species microarray reveals a protective role for stromal matrix metalloproteinase-12 in non-small cell lung cancer.
Cancer Res. 2006 Aug 15; 66(16):7968-75
This manuscript is a result of collaboration between many colleagues at Vanderbilt (including the Matrisian, Sinnamon, Fingleton, and Carbone labs as well as VMSR faculty and staff) and investigators at Wayne State University. Acuff et al designed a customized Affymetrix protease microarray (Hu/Mu ProtIn chip) designed to distinguish human and mouse genes to analyze the expression of proteases and protease inhibitors in lung cancer. Traditional microarrays using RNA from whole tumors cannot distinguish if genes are expressed from tumor cells or surrounding host cells, such as fibroblasts, endothelial cells, or inflammatory cells. The Hu/Mu ProtIn chip was designed to distinguish mouse and human proteases and protease inhibitors by generating oligonucleotides specific for either mouse or human genes. By using a xenograft approach, in which human tumor cells were injected into a mouse, the Hu/Mu ProtIn chip allowed the identification of genes transcribed by the tumor (human) and the host (mouse), allowing a better understanding of the cross-talk between proteases in the tumor and the surrounding microenvironment. Many candidate stromal proteases were detected using this model system. These results were compared to a data set of human lung adenocarcinoma specimens from the Carbone lab run on Affymetrix U133 Plus 2.0 arrays by the VMSR. MMP-12, MMP-13, and cathepsin K showed an increase in expression in human tumors compared with normal lung similar to that seen in the orthotopic model
- Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma, Shedden K, Taylor JM, Enkemann SA, Tsao MS, Yeatman TJ, Gerald WL, Eschrich S, Jurisica I, Giordano TJ, Misek DE, Chang AC, Zhu CQ, Strumpf D, Hanash S, Shepherd FA, Ding K, Seymour L, Naoki K, Pennell N, Weir B, Verhaak R, Ladd-Acosta C, Golub T, Gruidl M, Sharma A, Szoke J, Zakowski M, Rusch V, Kris M, Viale A, Motoi N, Travis W, Conley B, Seshan VE, Meyerson M, Kuick R, Dobbin KK, Lively T, Jacobson JW, Beer DG, Shedden K, Taylor JM, Enkemann SA, Tsao MS, Yeatman TJ, Gerald WL, Eschrich S, Jurisica I, Giordano TJ, Misek DE, Chang AC, Zhu CQ, Strumpf D, Hanash S, Shepherd FA, Ding K, Seymour L, Naoki K, Pennell N, Weir B, Verhaak R, Ladd-Acosta C, Golub T, Gruidl M, Sharma A, Szoke J, Zakowski M, Rusch V, Kris M, Viale A, Motoi N, Travis W, Conley B, Seshan VE, Meyerson M, Kuick R, Dobbin KK, Lively T, Jacobson JW, Beer DG
Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.
Nat Med. 2008 Jul 20; [Epub ahead of print] - Dutrow N, Nix DA, Holt D, Milash B, Dalley B, Westbroek E, Parnell TJ, Cairns BR
Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA-DNA hybrid mapping.
Nat Genet. 2008 Jul 20; [Epub ahead of print] - Cresta S, Sessa C, Catapano CV, Gallerani E, Passalacqua D, Rinaldi A, Bertoni F, Vigaṇ L, Maur M, Capri G, Maccioni E, Tosi D, Gianni L
Phase I study of bortezomib with weekly paclitaxel in patients with advanced solid tumours.
Eur J Cancer. 2008 Jul 17; [Epub ahead of print] - Wang PS, Chou FS, Bloomston M, Vonau MS, Saji M, Espinosa A, Pinzone JJ
Thiazolidinediones Downregulate Wnt/beta-Catenin Signaling Via Multiple Mechanisms in Breast Cancer Cells.
J Surg Res. 2008 Jun 27; [Epub ahead of print] - Ryan MC, Zeeberg BR, Caplen NJ, Cleland JA, Kahn AB, Liu H, Weinstein JN
SpliceCenter: a suite of web-based bioinformatic applications for evaluating the impact of alternative splicing on RT-PCR, RNAi, microarray, and peptide-based studies.
BMC Bioinformatics. 2008 Jul 18; 9(1):313 [Epub ahead of print]
- Katoh M
Cancer genomics and genetics of FGFR2 (Review).
Int J Oncol. 2008 Aug; 33(2):233-7 - Kim SK, Jang HR, Kim JH, Kim M, Noh SM, Song KS, Kang GH, Kim HJ, Kim SY, Yoo HS, Kim YS
CpG methylation in exon 1 of Transcription Factor 4 increases with age in normal gastric mucosa and is associated with gene silencing in intestinal type gastric cancers.
Carcinogenesis. 2008 Jul 16; [Epub ahead of print] - Vliem MJ, Ponsioen B, Schwede F, Pannekoek WJ, Riedl J, Kooistra MR, Jalink K, Genieser HG, Bos JL, Rehmann H
8-pCPT-2'-O-Me-cAMP-AM: An Improved Epac-Selective cAMP Analogue.
Chembiochem. 2008 Jul 16; [Epub ahead of print] - Wilson AJ, Byun DS, Nasser S, Murray L, Ayyanar K, Arango D, Figueroa M, Melnick A, Kao GD, Augenlicht LH, Mariadason JM
HDAC4 Promotes Growth of Colon Cancer Cells via Repression of p21.
Mol Biol Cell. 2008 Jul 16; [Epub ahead of print]
- Steinbrink S, Boutros M
RNAi Screening in Cultured Drosophila Cells.
Methods Mol Biol. 2008; 420:139-53 - Kawasaki G, Yanamoto S, Yoshitomi I, Yamada S, Mizuno A
Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion.
Int J Oral Maxillofac Surg. 2008 Jul 18; [Epub ahead of print] - Zhao W, Xu Y, Kong D, Liu R, Zhang Z, Jin C, Zhang Z, Xiu Y
Tissue-selective RNA interference in prostate cancer cell using prostate specific membrane antigen promoter/enhancer().
Urol Oncol. 2008 Jul 16; [Epub ahead of print]
News and Notes
- Previously analyzed data could benefit from a second look using new analysis techniques and software, which can uncover expression patterns, provide pathway analysis, or drug discovery information.
- Agilent arrays are now offered for CGH and gene expression analysis.
- Interested in miRNA detection? Exiqon miRCURY™ LNA microRNA Arrays offer high-quality miRNA data from total RNA - no fractionation required!
- Tiling arrays are a discovery tool for studying gene regulation, including mapping sites of protein/DNA interaction in ChIP experiments, discovering new RNA transcripts, and understanding DNA methylation or acetylation.
- VMSR functional genomics capabilities include RNAi and full-length cDNA libraries, with clones available to Vanderbilt researchers at a fraction of the cost of commercial websites. Synthetic RNAi libraries with specific focuses are also available, including Human Druggable Genome, Protein Kinase, Phosphatases, and GPCR screening libraries.
- The newest DNA Mapping arrays probe almost 1 million SNPs and an additional 1 million copy number analysis probes. High-throughput handling in the VMSR has yielded decreased costs, making genotyping affordable to any budget. Copy number analysis can be done on as little as one tumor or diseased sample, when compared to publicly available normal controls.
Selected papers of interest
Characterizing the cancer genome in lung adenocarcinoma.
Nature. 2007 Dec 6; 450(7171):893-8 [Epub 2007 Nov 4]
Weir et al present the results of a systematic copy number analysis of 371 lung adenocarcinoma tumors. Using the Affymetrix 250K SNP Mapping (Sty) array, they identify 57 significantly recurrent amplifications and deletions and present several candidate oncogenes.
Increased COX2 expression enhances tumor-induced osteoclastic lesions in breast cancer bone metastasis.
Clin Exp Metastasis. 2008; 25(4):389-400 [Epub 2007 Oct 27]
Li et al used Affymetrix expression arrays to identify genes involved in metastasis of breast cancer tumors to the bone. From the array data, they identified and then functionally verified the importance of COX2 to tumor metastasis.
RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia.
Blood. 2008 Feb 15; 111(4):2238-45 [Epub 2007 Nov 19]
Tyner et al report on the development of an RNAi screen to identify tyrosine kinase targets in specific cancer samples
