Adrian Ishkanian

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Department:	Cancer Genetics (@ the BCCRC since 1998)
Research Role:	Graduate Student/Postdoctoral Fellow Alumnus
Education:	M.Sc (Pathology and Laboratory Medicine), UBC, 2001 M.D., UBC, 2005
Birthplace:	Vancouver, British Columbia, Canada

Research Interests:

The identification of novel markers causal in oral tumorigenesis is critical for clinical diagnosis and intervention. I am currently studying oral premalignancies in order to identify these early stage genetic events. As such tissues are typically available as archival formalin-fixed paraffin-embedded biopsies I have modified the standard RAPD (Randomly Amplified Polymorphic DNA) fingerprinting technique to utilize this material. This modified assay (SMAL Scanning Minute Archival Lesions) enables reproducible high-density fingerprinting of specific cell populations dissected either manually or through LCM (Laser Capture Microdissection). Using this assay, I have currently identified novel genetic changes that parallel the oral cancer progression stages. Genetic instability on chromosomes 1, 2, 3, 5, 7, 10 and 20 has been observed in multiple dysplasias and tumors. Clustering of multiple alterations to one region of the genome has been observed, indicating candidate locations for novel gene identification. Genetic instability on chromosome 2, 5, 7 and 8 has been verified by LOH (loss of heterozygosity) analysis and fine mapping has identified candidate genes in these regions. Deletions and copy number increases contribute to alterations in the expression of tumor-suppressor genes and oncogenes, respectively. Fine mapping these genomic alterations by conventional LOH is labour intensive and requires large quantities of patient material. I am currently investigating an alternate approach termed array CGH. This technique uses comparative genomic hybridization of normal and disease tissue DNA against an ordered set of human BACs (Bacterial Artificial Chromosomes). Intensity variations between each arrayed BAC clone provide locus by locus information on DNA copy number. BAC contigs spanning multiple genomic regions of interest have been constructed for this purpose. Production and validation of each clone has been made possible through collaboration with the BCCA Genome Sequencing Centre. By modifying standard cDNA based microarray technology, we have built both nylon and glass-based BAC arrays covering every significant reported region of genetic instability in oral carcinogenesis. Hybridization of total genomic DNA from appropriate oral tissues to this Oral Cancer BAC Array will provides a unique method for comprehensive analysis of allelic imbalance in a single experiment, and the potential to fine map each region to a single BAC. We are currently applying this technology as a high-throughput method for fine mapping novel regions identified through SMAL fingerprinting.

Sites of Interest: Work

 Human Genome Project Working Draft at UCSC
 Project Ensembl
 The Genome Database
 Genome Sequencing Centre: Washington University in Saint Louis
 National Center for Biotechnology Information
 Microarray Centre at University Health Network, Ontario Cancer Institute
 Webcutter 2.0
 Genome Meetings Calender
 BAC PAC Resources: NCI
 Primer Tm Determination

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