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.
- Choi KJ, Lee JH, Kim KS, Kang S, Lee YS, Bae S
Identification of ELAVL4 as a modulator of radiation sensitivity in A549 non-small cell lung cancer cells.
Oncol Rep. 2011 Apr 13; [Epub ahead of print] - Sangoi AR, Fujiwara M, West RB, Montgomery KD, Bonventre JV, Higgins JP, Rouse RV, Gokden N, McKenney JK
Immunohistochemical Distinction of Primary Adrenal Cortical Lesions From Metastatic Clear Cell Renal Cell Carcinoma: A Study of 248 Cases.
Am J Surg Pathol. 2011 May; 35(5):678-686 - Moussay E, Kaoma T, Baginska J, Muller A, Van Moer K, Nicot N, Nazarov PV, Vallar L, Chouaib S, Berchem G, Janji B
The acquisition of resistance to TNFα in breast cancer cells is associated with constitutive activation of autophagy as revealed by a transcriptome analysis using a custom microarray.
Autophagy. 2011 Jul 1; 7(7) [Epub ahead of print] - Nordentoft I, Dyrskjot L, Bodker JS, Wild PJ, Hartmann A, Bertz S, Lehmann J, Orntoft TF, Birkenkamp-Demtroder K
Increased expression of Transcription Factor TFAP2 alpha correlates with chemosensitivity in advanced bladder cancer.
BMC Cancer. 2011 Apr 14; 11(1):135 [Epub ahead of print] - Colo AE, Simoes AC, Carvalho AL, Melo CM, Fahham L, Kowalski LP, Soares FA, Neves EJ, Reis LF, Carvalho AF
Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma.
BMC Med Genomics. 2011 Apr 13; 4(1):33 [Epub ahead of print]
- Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S, Wang C, Flomenberg N, Knudsen ES, Howell A, Pestell RG, Sotgia F, Lisanti MP
Ketones and lactate increase cancer cell "stemness," driving recurrence, metastasis, and poor clinical outcome in breast cancer: Achieving personalized medicine via Metabolo-Genomics.
Cell Cycle. 2011 Apr 15; 10(8) [Epub ahead of print] - Ned RM, Melillo S, Marrone M
Fecal DNA testing for Colorectal Cancer Screening: the ColoSure™ test.
PLoS Curr. 2011 Mar 22; 3:RRN1220 - Zeng H, Yu H, Lu L, Jain D, Kidd MS, Saif MW, Chanock SJ, Hartge P, Risch HA, for the PanScan Consortium,
Genetic Effects and Modifiers of Radiotherapy and Chemotherapy on Survival in Pancreatic Cancer.
Pancreas. 2011 Apr 7; [Epub ahead of print] - Zhang YZ, Zhang LH, Gao Y, Li CH, Jia SQ, Liu N, Cheng F, Niu DY, Cho WC, Ji JF, Zeng CQ
Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling.
World J Gastroenterol. 2011 Apr 7; 17(13):1710-7
- Lister A, Nedjadi T, Kitteringham NR, Campbell F, Costello E, Lloyd B, Copple IM, Williams S, Owen A, Neoptolemos JP, Goldring CE, Park BK
Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy.
Mol Cancer. 2011 Apr 13; 10(1):37 [Epub ahead of print] - Seyhan AA, Varadarajan U, Choe S, Liu Y, McGraw J, Woods M, Murray S, Eckert A, Liu W, Ryan TE
A genome-wide RNAi screen identifies novel targets of neratinib sensitivity leading to neratinib and paclitaxel combination drug treatments.
Mol Biosyst. 2011 Apr 12; [Epub ahead of print] - Gentile A, Lazzari L, Benvenuti S, Trusolino L, Comoglio PM
Ror1 Is a Pseudokinase That Is Crucial for Met-Driven Tumorigenesis.
Cancer Res. 2011 Apr 12; [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