Problem: Cancer is one of the most genetically complex conditions faced by modern medicine. Displaying a significant capacity to evolve in terms of its genomic make-up, malignant tumours can accumulate a variety of mutations depending upon the type, clinical stage and also in response to selective pressures such as anti-cancer therapies. Despite significant treatment advances, cancer remains the predominant cause of premature death, and was responsible for 28 percent of all UK deaths over a two-year period during 2007-2009; representing a higher proportion than coronary heart disease or stroke mortality (CRUK 2012). As such, cancer has remained a top research priority, with extensive resources currently being utilized to advance our understanding of the complex underlying heterogeneity of the disease.

Traditional approaches for research into tumor formation have revolved around histological classification, using karyotyping for the identification of gross chromosomal aberrations. However, considering the extensive depth of genomic analysis required, it is unsurprising that such techniques are no longer sufficient for producing data at the resolution required for progressing cancer research. Consequently, molecular methods, such as microarray analysis, have been used for the identification of genetic markers associated with disease predication, progression and prognosis.

Microarrays being loaded into a scanner at OGT’s highthroughput genomic services facility.

Solution: Microarrays are a well-established technique for genomic research and have proven an important tool for delving into the complex genetic basis of cancer. Ideal for large-scale screening, microarrays provide whole genome coverage in a cost-effective manner. Additionally, when utilizing an expert service provider, samples can be processed with relatively high throughput.

Requiring knowledge of the genome sequence for probe design, microarrays have been significantly more valuable since the completion of the human genome project at the turn of the millennium. With the opportunity for flexible array layouts and probe design, including the ability to generate custom arrays, researchers have significant scope to scan the genome for sequence variations or to analyze gene expression profiles related to disease.

The Cytosure Haematological +SNP array combines aCGH and SNP probes for accurate detection of CNV and LOH.The latest developments in microarray technology are further advancing the capacity of microarrays for cancer research applications. For example, Oxford Gene Technology’s (OGT) latest line of arrays combine array comparative genomic hybridization (aCGH) and SNP probes on a single chip, with hybridization conditions optimized to allow both analysis techniques to be performed during a single experiment. This permits the simultaneous detection of larger genetic aberrations such as copy number variants (CNVs), alongside smaller variations and loss of heterozygosity (LOH). For example, OGT’s CytoSure™ Haematological Cancer +SNP array is optimized for the study of a number of haematological malignancies.

Of further benefit to researchers are the current collaborative efforts between commercial technology providers and academic experts, where combining knowledge and expertise permits informed, rational design of specific arrays. OGT has recently worked alongside Professor Jacqueline Schoumans, Head of the Cancer Cytogenetic Unit at the University of Lausanne and a world leader in cancer cytogenetics. This led to the development of a combined aCGH and SNP array targeting haematological and solid tumours. Importantly, this new CytoSure™ Cancer +SNP array enables the use of a matched reference from the same sample source in the same hybridization reaction, for a more accurate, direct comparison. With these developments, microarrays remain a versatile and efficient tool for research into the genetic basis of cancer, providing whole genome coverage for the accurate detection of CNVs and LOH across many samples. Microarray analysis is an established, well-practiced procedure, with the majority of clinical labs having accumulated all the necessary array equipment, training and experience. As such, microarrays often provide the initial go-to solution for cancer research projects

CytoSure™ products are for research use only; not for use in diagnostic procedures.

For more information, please visit www.ogt.com/cancer