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Blood, 15 January 2008, Vol. 111, No. 2, pp. 776-784. Prepublished online as a Blood First Edition Paper on September 21, 2007; DOI 10.1182/blood-2007-05-088310.
NEOPLASIA Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray1 Department of Hematology, Oncology, Cedars-Sinai Medical Center/University of California at Los Angeles School of Medicine; 2 Regeneration Medicine of Hematopoiesis, University of Tokyo, School of Medicine, Tokyo, Japan; 3 Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School (MHH), Hannover, Germany; 4 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5 Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany; 6 Department of Pediatric Hematology and Oncology, Justus Liebig University, Gieβen, Germany; 7 Department of Hematology, Oncology and Tumor Immunology, Robert-Rössle-Clinic at the HELIOS-Clinic Berlin-Buch, Charité, Berlin, Germany; and 8 Department of Pediatrics, University of Kiel, Kiel, Germany
Pediatric acute lymphoblastic leukemia (ALL) is a malignant disease resulting from accumulation of genetic alterations. A robust technology, single nucleotide polymorphism oligonucleotide genomic microarray (SNP-chip) in concert with bioinformatics offers the opportunity to discover the genetic lesions associated with ALL. We examined 399 pediatric ALL samples and their matched remission marrows at 50 000/250 000 SNP sites using an SNP-chip platform. Correlations between genetic abnormalities and clinical features were examined. Three common genetic alterations were found: deletion of ETV6, deletion of p16INK4A, and hyperdiploidy, as well as a number of novel recurrent genetic alterations. Uniparental disomy (UPD) was a frequent event, especially affecting chromosome 9. A cohort of children with hyperdiploid ALL without gain of chromosomes 17 and 18 had a poor prognosis. Molecular allelokaryotyping is a robust tool to define small genetic abnormalities including UPD, which is usually overlooked by standard methods. This technique was able to detect subgroups with a poor prognosis based on their genetic status.
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