Abstract
Pediatric acute lymphoblastic leukemia (ALL) is a malignant disease resulting from accumulation of genetic alterations, and various genomic abnormalities are reported. Although these genetic lesions are important in leukemia initiation, they are insufficient to elucidate an entire etiology. Recently, we have developed a novel algorithm, CNAG/AsCNAR, to detect copy number alteration and allelic composition using SNP-genotyping microarrays, without dependence on the availability of self germ-line DNA. This robust algorithm also enabled sensitive detection of loss of heterozygosity (LOH) even in the primary samples contaminated by 70-80% of normal cells by finding subtle distortions in allele-specific signals (Molecular allelo-karyotyping). We examined 399 pediatric ALL samples using an SNP-chip platform, and discovered a detailed profile of genomic abnormalities. Molecular allelo-karyotyping also showed that alterations of genes related to B-cell development and differentiation, including PAX5, contributed to leukemogenesis.
