Applying microarray and sequencing technologies to cancer studies

Tuesday 30 August 2011

Researchers are increasingly using high-throughput genomic technologies to elucidate the genetic basis of many forms of cancer — due to their capacity for rapid and cost-effective delivery of informative results. However, such studies can prove challenging due to the sheer volume and complexity of the data generated. Oxford Gene Technology’s (OGT) Genefficiency™ Genomic Services offers an integrated range of reliable genomic services — including the design and service of microarray and targeted sequencing projects. More importantly, our bioinformatics expertise ensures we deliver meaningful results rather than insurmountable data sets, allowing you to characterise and identify potential biomarkers for your cancer of interest.

Array comparative genomic hybridisation (aCGH)

aCGH platforms, which allow detection of known and de novo copy number variation (CNV) present in a cell or tissue, play an important role in genome analysis and have had a major impact on the identification of genetic disorders and cancer, accelerating CNV discovery for many diseases¹. Furthermore, genome-wide association studies (GWAS) using oligonucleotide aCGH are considered the gold-standard for CNV detection². OGT offers a choice of pre-designed or custom arrays to achieve maximum resolution over either the whole genome or particular regions of interest. OGT has developed a database with over 20 million optimised aCGH probes, which can be used to create a custom array to your chosen region(s) of interest. An extensive range of array formats are available ranging from 1 million probes on a single array down to 15,000 probes in 8 separate array areas, allowing you to create the most suitable and cost-effective design for your study.

Genefficiency aCGH services are ISO/IEC 17025:2005 accredited by the United Kingdom Accreditation Service (UKAS) — underlining the superior level of expertise and quality control in OGT’s laboratories. In addition, OGT was the first company to be awarded High-Throughput Certified Service Provider status for Agilent microarrays.

Gene expression

Many studies have used microarrays to identify gene expression signatures allowing patient stratification based upon disease subtype^3,4, prognosis and survival — thus offering the potential of improved clinical management⁵. OGT offers both pre-designed arrays and custom array design and servicing, enabling sensitive genome-wide gene expression analysis, which can be customised to your specific cancer(s), genes or research projects of interest. Our experienced bioinformatics team can provide expert custom array design, in a format to suit your specific requirements and budget — plus bespoke data analysis services ensuring delivery of meaningful results.

Methylation

Studies have demonstrated the utility of microarrays for analysing DNA methylation and have shown the close relationship between methylation and transcription, in which epigenetic changes contribute to the carcinogenic process. De novo methylation of CpG islands is a common occurrence in human cancers. A recent study by Michaelson-Cohen et al, illustrated how methylation of CpG islands causes silencing of genes that have a role in cell differentiation and function. Therefore methylation status may act as a potential biomarker for diagnosis, prognosis, and treatment responsiveness⁶. Our experienced molecular biology, genomic biomarker and bioinformatics teams provide array design and sample processing through to bespoke data analysis, ensuring delivery of meaningful results. Methylation arrays are available for both promoter regions and CpG islands. In addition, our expert team is on hand to discuss the optimal sample preparation methods and experimental design.

microRNA (miRNA)

Recent evidence discovered through miRNA microarray studies suggest an important role for miRNA in initiation, progression and metastasis of human cancers. OGT offers arrays designed using the latest miRBase release increasing the likelihood of discovering biologically relevant results. Our experienced molecular biology and bioinformatics teams provide array design and sample processing through to bespoke data analysis, ensuring delivery of meaningful results. In addition, our expert team is on hand to discuss the optimal sample preparation methods and experimental design most suitable for your area of cancer research.

Next Generation Sequencing

Genefficiency Targeted Sequencing Services provide an additional, high-resolution technique for characterising your cancer of interest.

A recent BBSRC⁷ (Biotechnology and Biological Sciences Research Council) report, concluded that data analysis is the main bottleneck in sequencing, often taking many months at considerable cost to get from raw data to intelligible results. Genefficiency Targeted Sequencing Services are designed to be different, leading you all the way from project conception to high-quality results. Our expert and comprehensive project design and analysis solutions are tailored to your specific needs allowing you to discover, not just sequence.

We offer expert capture and enrichment of your regions of interest (whole exome or custom library) this critical step improves the uniformity of sequencing coverage and maximises the likelihood of finding biologically relevant variants. In addition, we provide expert advice on the sequencing coverage required for your tumour sample(s) and utilise industry-leading sequencing platforms to ensure the highest quality results.

Contact our experienced team to discuss your specific cancer research project and find out how we can deliver high-quality, meaningful results.

References

Shaffer, L.G. et al (2007) The identification of micro deletion syndromes and other chromosome abnormalities: cytogenetic methods of the past, new technologies for the future. American Journal of Medical Genetics 145C, 335-345
Carter, N.P. (2007) Methods and strategies for analyzing copy number variation using DNA microarrays. Nature Genetics 39, S16-S21
Sørlie, T. et al (2001) Gene expression patterns of breast carcinomas distinguish tumour subclasses with clinical implications. Proceedings of the National Academy of Sciences of the United States of America 98, 19869-10874
Zhan, F. et al (2006) The molecular classification of multiple myeloma. Blood 108, 2020–2028
Schwalbe, E.C. et al (2011) Rapid diagnosis of medulloblastoma molecular subgroups. Clinical Cancer Research 17, 1883-1894
Michaelson-Cohen, R. et al (2011) Genome-wide de novo methylation in epithelial ovarian cancer. National Journal of Gynaecological Cancer 2011 Feb: 21 (2) 269-79
BBSRC Next generation sequencing review [online] available online at http://www.bbsrc.ac.uk/organisation/policies/reviews/scientific-areas/1102-next-generation-sequencing-review.aspx [Accessed 15th February 2011]