Application

At present, there are two main trends in DNA microarray fabrication. The first one is high-density of microarray that more than 1 million probes can be mounted onto every square cm by in situ synthesis. This might help the researches to manifest the whole genome analysis of one species on a single microarray. The second one is minimization of reaction systems, which refers to the minimization of required testing samples of the microarray. The minimum starting requirement of total RNA or DNA for DNA microarray hybridization is of nanogram level, which makes it possible to study the expression profile of a single cell. This is especially useful in iPSCs (induced pluripotent stem cells) research field.

A study using DNA microarray technology was carried out by Friend and colleagues in 2002, who provide a good example of the use of expression profiling by DNA microarray to improve breast cancer classification and therapy. Many breast-cancer patients receive unnecessary chemotherapy or hormonal treatment for possible tumor spread after removal of a primary tumor. Classical histopathological and clinical criteria are insufficient to determine which patients need this adjuvant treatment.

Friend and colleagues analysed primary breast tumor from a mix of patients who developed metastases or remained disease-free after 5 years, using DNA microarrays to study the gene expression profiles. They were able to identify 70 genes significantly associated with disease outcome, and developed a prognosis classifier based on this microarray study. This constituted a powerful tool for tailoring treatment to those patients at risk of recurring disease, and avoiding unnecessary treatment and the associated costs in patient quality of life and health-care expenditure.

Yongtao Xue-Franzen. 2009. DNA microarray approaches to understanding the regulation and evolution of gene expression networks. Stockholm, Sweden. Karolinka University Press

HAN ZeGuang’s team from the National Human Genome Center at Shanghai reported on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive hepatocelluar carcinoma through a cDNA microarray containing 12393 genes/ESTs. Integrated data identified 2253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further study. The altered transcriptome profiles in hepatocelluar carcinoma could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of hepatocelluar carcinoma. In 2002, ZHANG Xu’s team from Institute of Neuroscience, Chinese Academy of Sciences used the gene expression microarray to study the gene expression of dorsal root ganglia in the rat peripheral nerve injury model. They tried to elucidate the gene expression profile by using a cDNA microarray with 7523 genes and found a group of genes related to nerve injury and pain which could be considered as potential drug targets. The results also suggested the molecular mechanisms of Gabapentin engaged in the clinical therapy for pain

Gunderson et al. utilized DNA microarray to detect SNP locus in human genome. These data showed high consistence with the traditionally PCR-based technique. Amplichip CYP450 testing chip made by Roche was approved by FDA to enter the clinical trials in 2005. This chip could be used to analyze polymorphism loci that may determine the activity of cytochrome oxidase and predict whether the drug metabolism rate is high or low in patients. That was the first SNP microarray used in clinical. Later on, Burton et al. examined 14500 SNP loci between autoimmunity disease patients and healthy individuals by microarray. The study included 1000 patients suffering four diseases and 1500 health individuals as the controls

In 2006, researchers from Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai analyzed the relevance between genome copy number alterations and transcriptional expression of hepatitis B virus associated with human hepatocellular carcinoma through comparative genomic hybridization (aCGH) and gene expression profiling approaches jointly. This work provided new insights into the novel genetic mechanisms in hepatocarcinogenesis associated with hepatitis B virus. Carter et al. reported that up to 12% of the human genome and thousands of genes are variable in copy number. This diversity is likely to be responsible for a significant proportion of normal phenotypic variation. The discovery is far beyond the forecast ever before. Lee et al. reported that mental retardation was genotyped using comparative genomic hybridization (aCGH). One deletion of chromosome region 15q13.3 was found in the patients, and the work was published in Nature Genetics.

X. K. Teng., H.S. Xiao., 2009. Perspectives of DNA microarray and next-generation DNA sequencing technologies. Sci China Ser C-Life Sci 52 (1): 7-16