Joshua Schiffman, MD
The University of Utah's Joshua Schiffman, MD, discusses the use of molecular inversion probe (MIP) technology for studying copy number alterations in pediatric cancers
Scientists at the University of Utah, led by Dr. Joshua Schiffman, are using MIP technology to identify unique genetic aberrations that can distinguish between different types of pediatric cancers. Their work has uncovered patterns of copy number aberrations and regions of allelic imbalance that could be used to guide risk stratification and future treatment.
In 2009, Dr. Schiffman collaborated with Affymetrix using a 24K MIP panel and GeneChip® 30K Universal Tag Arrays to analyze 45 pediatric leukemia samples in order to detect unique copy number aberrations. Their study identified 69 regions of copy number changes, including unique patterns of copy number loss in samples with a deletion of the CDKN2A gene. These patterns differentiated between two similar subtypes of acute lymphoblastic leukemia (ALL), precursor B-cell ALL and precursor T-cell ALL. Recently, Schiffman and colleagues used Affymetrix MIP Copy Number Services to perform a genome-wide analysisof copy number alterations in different malignancy grades of pediatric astrocytomas. The study identified several genomic amplifications that characterized the different tumor grades. Specifically, the study revealed distinct BRAF gene rearrangements that occurred in grade 1 versus grade 2 to 4 tumors and indicated BRAF mutation as a frequent mutation target in pediatric astrocytomas. They also found that BRAF mutations were significantly associated with homozygous CDKN2A deletions, suggesting the possibility of a new subset of pediatric astrocytomas.
"With the MIP assay, we can easily correlate patient outcome with higher copy numbers," said Schiffman. "Once we collect enough samples and enough outcome data, we"ll better understand the relationship between high copy number value and clinical outcome in many different types of cancer." Schiffman recently spoke with Jessica Parra, Associate Marketing Manager at Affymetrix, about his use of the MIP copy number platform to study different forms of pediatric cancers. The two discussed:
- The advantages of being able to analyze formalin-fixed, paraffin-embedded (FFPE) samples
- The MIP copy number platform design and the linear dynamic range of the assay
- The clinical importance of being able to identify copy number changes that can characterize different forms of pediatric cancers
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