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
Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1.
Nat Genet. 2009 Mar; 41(3):324-8 [Epub 2009 Feb 15]
Wei Zheng and colleagues performed a large, multi-stage genomewide association study on breast cancer in Chinese women. They present a novel risk variant on 6q25.1, near the ESR1 gene, and verified it in a cohort of European ancestry. In the first stage of the study, 1,374 cases and 1,402 controls were genotyped at the VMSR using the Affymetrix Genomewide SNP 6.0 array. In addition to the 900,000 SNPs available on that array, Zheng et al imputed a further 1.14 million genotypes using HapMap data. From this initial stage, they identified 29 SNPs as 'promising', and genotyped them in an independent set of 1,554 cases and 1,576 controls using the Sequenom platform. Four SNPs were identified in the second stage as highly associated with breast cancer, and these four SNPs were genotyped in a third stage of 3,472 cases and 900 controls. In each stage individually, and in a pooled analysis of all three stages, rs2046210 showed very consistent and strong association. A final verification was performed on a cohort of 1,590 cases and 1,466 controls of European ancestry, which yielded results consistent with the three Chinese cohorts.
- Weigelt B, Baehner FL, Reis-Filho JS
The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade.
J Pathol. 2009 Nov 19; [Epub ahead of print] - Thomson TA, Zhou C, Chu C, Knight B
Tissue Microarray for Routine Analysis of Breast Biomarkers in the Clinical Laboratory.
Am J Clin Pathol. 2009 Dec; 132(6):899-905 - Derycke MS, Andersen JD, Harrington KM, Pambuccian SE, Kalloger SE, Boylan KL, Argenta PA, Skubitz AP
S100A1 Expression in Ovarian and Endometrial Endometrioid Carcinomas Is a Prognostic Indicator of Relapse-Free Survival.
Am J Clin Pathol. 2009 Dec; 132(6):846-856 - Tang L, Yang J, Ng SK, Rodriguez N, Choi PW, Vitonis A, Wang K, McLachlan GJ, Caiazzo RJ Jr, Liu BC, Welch WR, Cramer DW, Berkowitz RS, Ng SW
Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer.
Eur J Cancer. 2009 Nov 16; [Epub ahead of print] - Saeki Y, Endo T, Ide K, Nagashima T, Yumoto N, Toyoda T, Suzuki H, Hayashizaki Y, Sakaki Y, Okada-Hatakeyama M
Ligand-specific sequential regulation of transcription factors for differentiation of MCF-7 cells.
BMC Genomics. 2009 Nov 20; 10(1):545 [Epub ahead of print]
- Knutsen T, Padilla-Nash HM, Wangsa D, Barenboim-Stapleton L, Camps J, McNeil N, Difilippantonio MJ, Ried T
Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines.
Genes Chromosomes Cancer. 2009 Nov 19; [Epub ahead of print] - Shi T, Weerasekera R, Yan C, Reginold W, Ball H, Kislinger T, Schmitt-Ulms G
Method for the Affinity Purification of Covalently Linked Peptides Following Cyanogen Bromide Cleavage of Proteins.
Anal Chem. 2009 Nov 19; [Epub ahead of print] - Glinskii AB, Ma J, Ma S, Grant D, Lim CU, Sell S, Glinsky GV
Identification of intergenic trans-regulatory RNAs containing a disease-linked SNP sequence and targeting cell cycle progression/differentiation pathways in multiple common human disorders.
Cell Cycle. 2009 Dec 17; 8(23) [Epub ahead of print] - Aparicio SA, Huntsman DG
Does massively parallel DNA resequencing signify the end of histopathology as we know it?
J Pathol. 2009 Nov 17; [Epub ahead of print]
- Saeki Y, Endo T, Ide K, Nagashima T, Yumoto N, Toyoda T, Suzuki H, Hayashizaki Y, Sakaki Y, Okada-Hatakeyama M
Ligand-specific sequential regulation of transcription factors for differentiation of MCF-7 cells.
BMC Genomics. 2009 Nov 20; 10(1):545 [Epub ahead of print] - Liu XX, Yao C, Zhang H, Wang SM, Wang SM
[Construction of an expression vector carrying short hairpin RNA targeting hTERT gene and its effects on breast cancer cell telomerase activity and proliferation in vivo.]
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Nov 20; 29(11):2187-2190 - Omerovic J, Clague MJ, Prior IA
Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras mutated cancer cells.
Biochem J. 2009 Nov 19; [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
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
Acuff et al designed a custom Affymetrix protease array to distinguish human and mouse genes. By then using a xenograft approach in which human lung tumor cells are injected into a mouse, they could identify the 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. 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
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.
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
