title: Novel cryptic chromosomal rearrangements in childhood acute lymphoblastic leukemia detected by multiple color fluorescent in situ hybridization.
abstract: OBJECTIVE
  It is often difficult to obtain good karyotypes of cells from children with acute lymphoblastic leukemia (ALL) because of poor morphology and spreading. Detailed karyotyping can be further hampered by the presence of multiple rearrangements. Our objective was to search for cryptic rearrangements in childhood ALL.
  
  
  METHODS
  A series of eight cases of childhood ALL with at least two structural defects were selected and studied by multiple color fluorescent in situ hybridization (M-FISH).
  
  
  RESULTS
  Four previously not reported translocations were detected: a t(14;20) (q32;q11.2) in a 3-year old girl with T-ALL, a cryptic t(7;11)(q35;q24) in association with a t(1;14)(p32;q32) in a patient with T-ALL and two translocations possibly involving the same 6q26 region on the distal end of the long arm of chromosome 6. Further FISH analysis on the t(7;11) indicated rearrangement of the TCRB locus at 7q35 suggesting that this t(7;11) leads to overexpression of an as yet unidentified gene at 11q24. This observation also triggered further screening for TCRB rearrangements in T-ALL. FISH analysis of the t(14;20) with an IGH locus-specific probe provided evidence for an unusual rearrangement of the IGH gene, in the variable gene segment region. Finally, we also observed cryptic insertions of AF4 and ETV6 in combination with complex rearrangements, leading to MLL/AF4 and ETV6/RUNX1 gene fusions.
  
  
  CONCLUSIONS
  This study underscores the importance and power of M-FISH analysis in unraveling complex karyotypes and identifying cryptic chromosomal rearrangements. It also sheds some light on the implication of cryptic TCRB rearrangements in T-ALL.
authors.affiliation: Center for Medical Genetics, University Hospital Ghent, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Barbara
authors.initials: B
authors.lastname: Cauwelier
authors.forename: Heidi
authors.initials: H
authors.lastname: Van Limbergen
authors.forename: Nurten
authors.initials: N
authors.lastname: Yigit
authors.forename: Jan
authors.initials: J
authors.lastname: Philippé
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007621:Karyotyping / Q000379:methods; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*