Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray

Blood. 2008 Jan 15;111(2):776-84. doi: 10.1182/blood-2007-05-088310. Epub 2007 Sep 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 9 / genetics*
  • Clinical Trials as Topic
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • ETS Translocation Variant 6 Protein
  • Female
  • Gene Deletion*
  • Humans
  • Infant
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Ploidies
  • Polymorphism, Single Nucleotide*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-ets / genetics*
  • Repressor Proteins / genetics*
  • Retrospective Studies

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins