title: The neuroblastoma and ganglion components of nodular ganglioneuroblastoma are genetically similar: evidence against separate clonal origins.
abstract: Nodular ganglioneuroblastoma is characterized by a macroscopic nodule of neuroblastoma within a ganglioneuromatous component. These two components have been considered to originate from separate clones, with the neuroblastoma clone accounting for the clinical behavior of nodular ganglioneuroblastoma. In order to investigate the clonal origin of the cellular components (neuroblasts, ganglion cells, and Schwann cells) of nodular ganglioneuroblastoma, paraffin-embedded tumor samples from eight cases were analyzed by single nucleotide polymorphism array and in situ hybridization. DNA was extracted separately from neuroblastomatous and ganglioneuromatous areas. By in situ hybridization, MYCN gain (4-10 gene copies/nucleus) was detected in 7/8 neuroblastoma samples. In ganglioneuromatous regions, gains were also detected in ganglion cells but not in Schwann cells. Single-nucleotide polymorphism array studies identified chromosome losses (11q and 14q) and gains (12, 13q, 17q and 18q) in the neuroblastoma component, whereas the ganglioneuromatous component showed fewer or no genetic alterations. There were no unique copy number changes distinguishing nodular ganglioneuroblastoma from other subtypes of neuroblastoma. By in situ hybridization, ganglion cells but not Schwann cells showed the same alterations detected in neuroblasts. Thus, neuroblasts and ganglion cells in nodular ganglioneuroblastoma are genetically related and may arise from the same clone. In contrast, the Schwann cells have a different origin and may be derived from a non-neoplastic neural crest precursor. Our results suggest that the clinical behavior of nodular ganglioneuroblastoma cannot be explained by the presence of separate clones with distinct genetic signatures.
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Angelini
authors.affiliation: 1] Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada [2] Department of Pediatrics, University of Toronto, University of Toronto, Toronto, ON, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baruchel
authors.affiliation: Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Paula
authors.initials: P
authors.lastname: Marrano
authors.affiliation: 1] Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada [2] Department of Pediatrics, University of Toronto, University of Toronto, Toronto, ON, Canada.
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Irwin
authors.affiliation: 1] Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thorner
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D018305:Ganglioneuroblastoma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
references.citation: N Engl J Med. 2010 Sep 30;363(14):1313-23
references.pmid: 20879880
references.citation: Oncogene. 2008 May 8;27(21):3066-71
references.pmid: 18071318
references.citation: J Clin Oncol. 2006 Feb 1;24(4):695-9
references.pmid: 16446343
references.citation: Br J Cancer. 2007 Jul 16;97(2):238-46
references.pmid: 17579628
references.citation: Cancer. 2001 Nov 15;92(10):2699-708
references.pmid: 11745206
references.citation: J Clin Oncol. 2005 Sep 20;23(27):6459-65
references.pmid: 16116153
references.citation: Cancer. 1999 Jul 15;86(2):364-72
references.pmid: 10421273
references.citation: Nature. 1983 Sep 15-21;305(5931):245-8
references.pmid: 6888561
references.citation: Lancet. 2007 Jun 23;369(9579):2106-20
references.pmid: 17586306
references.citation: Pediatr Blood Cancer. 2009 Oct;53(4):563-9
references.pmid: 19530234
references.citation: Am J Surg Pathol. 2006 May;30(5):635-42
references.pmid: 16699319
references.citation: Cancer. 2000 Sep 1;89(5):1150-61
references.pmid: 10964346
references.citation: J Pathol. 2005 Nov;207(3):346-57
references.pmid: 16178058
references.citation: Eur J Cancer. 2012 May;48(8):1185-91
references.pmid: 22137163
references.citation: Eur J Cancer. 1995;31A(4):429-34
references.pmid: 7576940
references.citation: Genes Chromosomes Cancer. 2007 Oct;46(10):936-49
references.pmid: 17647283
references.citation: BMC Genomics. 2008 Jul 29;9:353
references.pmid: 18664255
references.citation: J Clin Oncol. 2009 Jan 10;27(2):289-97
references.pmid: 19047291
references.citation: Science. 1984 Jun 8;224(4653):1121-4
references.pmid: 6719137
references.citation: J Clin Oncol. 2009 Mar 1;27(7):1026-33
references.pmid: 19171713
references.citation: Carcinogenesis. 2004 Sep;25(9):1599-609
references.pmid: 15090470
references.citation: Diagn Mol Pathol. 2008 Mar;17(1):3-13
references.pmid: 18303412
references.citation: Pediatr Pathol. 1993 Nov-Dec;13(6):787-96
references.pmid: 8108298
references.citation: N Engl J Med. 1996 Jun 6;334(23):1505-11
references.pmid: 8618605
references.citation: BMC Genomics. 2004 Sep 20;5:70
references.pmid: 15380028
references.citation: J Natl Cancer Inst. 1984 Aug;73(2):405-16
references.pmid: 6589432
references.citation: Am J Pathol. 2005 Mar;166(3):891-900
references.pmid: 15743800
references.citation: Cancer. 2001 Nov 1;92(9):2451-61
references.pmid: 11745303
references.citation: N Engl J Med. 1985 Oct 31;313(18):1111-6
references.pmid: 4047115
references.citation: Cancer Res. 2001 Sep 15;61(18):6892-8
references.pmid: 11559566
references.citation: Cancer Genet Cytogenet. 2002 Jan 1;132(1):36-40
references.pmid: 11801306
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):4-12
references.pmid: 14734444
references.citation: Br J Cancer. 2002 Apr 8;86(7):1110-6
references.pmid: 11953858
references.citation: Br J Cancer. 2009 May 5;100(9):1471-82
references.pmid: 19401703
references.citation: Genes Chromosomes Cancer. 2006 Dec;45(12):1130-42
references.pmid: 16958102
references.citation: Cancer Genet Cytogenet. 2007 Aug;177(1):20-9
references.pmid: 17693187
references.citation: J Clin Oncol. 1998 Jun;16(6):2007-17
references.pmid: 9626197
references.citation: Genes Chromosomes Cancer. 2008 Oct;47(10):819-34
references.pmid: 18553563
references.citation: J Clin Oncol. 2005 Apr 1;23(10):2280-99
references.pmid: 15800319
references.citation: N Engl J Med. 2010 Jun 10;362(23):2202-11
references.pmid: 20558371
references.citation: Cancer. 2003 Nov 15;98(10):2274-81
references.pmid: 14601099
references.citation: Pediatr Dev Pathol. 2000 Mar-Apr;3(2):184-99
references.pmid: 10679039
references.citation: Med Pediatr Oncol. 2000 Dec;35(6):534-7
references.pmid: 11107110
references.citation: J Clin Oncol. 2009 Jan 20;27(3):365-70
references.pmid: 19047282