title: Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.
abstract: Neuroblastoma (NB) is a common and often lethal cancer of early childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents ≥ 10 y. There is increasing evidence that NB has unique biology and an chronic disease course in older children and adolescents, but ultimately dismal survival.
  
  
  
  We describe a rare constitutional 3p26.3 terminal microdeletion which occurred in an adolescent with NB, with apparently normal phenotype without neurocognitive defects. We evaluated the association of expression of genes involved in the microdeletion with NB patient outcomes using R2 platform. We screened NB patient's tumor cells for CHL1 protein expression using immunofluorescence.
  
  
  
  Constitutional and tumor DNA were tested by array-comparative genomic hybridization and single nucleotide-polymorphism-array analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb sub-microscopic constitutional terminal 3p deletion that extended to band p26.3. The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1 genes were hemizygously deleted, each of these genes encode neuronal cell adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB patients, whereas low CHL1 expression characterized 417 NB patients having worse overall survival. CHL1 protein expression on tumor cells from the patient was weaker than positive control.
  
  
  
  This is the first report of a constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p, indicative of the presence of one or more tumor suppressor genes in this region, occur frequently in neuroblastoma, our results pave the way to the identification of one putative NB suppressor genes mapping in 3p26.3.
authors.affiliation: a Laboratorio di Oncologia , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pezzolo
authors.affiliation: b Laboratorio di Anatomia Patologica , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Angela Rita
authors.initials: AR
authors.lastname: Sementa
authors.affiliation: c Laboratorio di Genetica Molecolare , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Lerone
authors.affiliation: d Laboratorio di Biologia Molecolare , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Morini
authors.affiliation: a Laboratorio di Oncologia , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Ognibene
authors.affiliation: b Laboratorio di Anatomia Patologica , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Defferrari
authors.affiliation: b Laboratorio di Anatomia Patologica , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Mazzocco
authors.affiliation: e Dipartimento di Emato-Oncologia , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.affiliation: e Dipartimento di Emato-Oncologia , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Gigliotti
authors.affiliation: e Dipartimento di Emato-Oncologia , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.affiliation: f Area Immunologica Ospedale Pediatrico Bambino Gesù , Roma.
authors.forename: Vito
authors.identifier: 0000-0003-0528-9563
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: d Laboratorio di Biologia Molecolare , Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Varesio
mesh_terms: D000293:Adolescent; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
keywords: 3p terminal deletion syndrome; 3p26.3 microdeletion; Array-CGH; germline structural chromosomal abnormalities; neuroblastoma