title: Large scale copy number variation (CNV) at 14q12 is associated with the presence of genomic abnormalities in neoplasia.
abstract: BACKGROUND
  Advances made in the area of microarray comparative genomic hybridization (aCGH) have enabled the interrogation of the entire genome at a previously unattainable resolution. This has lead to the discovery of a novel class of alternative entities called large-scale copy number variations (CNVs). These CNVs are often found in regions of closely linked sequence homology called duplicons that are thought to facilitate genomic rearrangements in some classes of neoplasia. Recently, it was proposed that duplicons located near the recurrent translocation break points on chromosomes 9 and 22 in chronic myeloid leukemia (CML) may facilitate this tumor-specific translocation. Furthermore, approximately 15-20% of CML patients also carry a microdeletion on the derivative 9 chromosome (der(9)) and these patients have a poor prognosis. It has been hypothesised that der(9) deletion patients have increased levels of chromosomal instability.
  
  
  RESULTS
  In this study aCGH was performed and identified a CNV (RP11-125A5, hereafter called CNV14q12) that was present as a genomic gain or loss in 10% of control DNA samples derived from cytogenetically normal individuals. CNV14q12 was the same clone identified by Iafrate et al. as a CNV. Real-time polymerase chain reaction (Q-PCR) was used to determine the relative frequency of this CNV in DNA from a series of 16 CML patients (both with and without a der(9) deletion) together with DNA derived from 36 paediatric solid tumors in comparison to the incidence of CNV in control DNA. CNV14q12 was present in approximately 50% of both tumor and CML DNA, but was found in 72% of CML bearing a der(9) microdeletion. Chi square analysis found a statistically significant difference (p <or= 0.001) between the incidence of this CNV in cancer and normal DNA and a slightly increased incidence in CML with deletions in comparison to those CML without a detectable deletion.
  
  
  CONCLUSIONS
  The increased incidence of CNV14q12 in tumor samples suggests that either acquired or inherited genomic variation of this new class of variation may be associated with onset or progression of neoplasia.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. ilanbraude@hotmail.com
authors.forename: Ilan
authors.initials: I
authors.lastname: Braude
authors.forename: Bisera
authors.initials: B
authors.lastname: Vukovic
authors.forename: Mona
authors.initials: M
authors.lastname: Prasad
authors.forename: Paula
authors.initials: P
authors.lastname: Marrano
authors.forename: Stefanie
authors.initials: S
authors.lastname: Turley
authors.forename: Dwayne
authors.initials: D
authors.lastname: Barber
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D015331:Cohort Studies; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods