title: A cluster of genes located in 1p36 are down-regulated in neuroblastomas with poor prognosis, but not due to CpG island methylation.
abstract: BACKGROUND
  A common feature of neuroblastoma tumours are partial deletions of the short arm of chromosome 1 (1p-deletions). This is indicative of a neuroblastoma tumour suppressor gene being located in the region. Several groups including our have been studying candidate neuroblastoma genes in the region, but no gene/genes have yet been found that fulfil the criteria for being a neuroblastoma tumour suppressor. Since frequent mutations have not been detected, we have now analyzed the expression and promoter CpG island methylation status of the genes UBE4B, KIF1B, PGD, APITD1, DFFA and PEX14 in the 1p36.22 region in order to find an explanation for a possible down-regulation of this region.
  
  
  RESULTS
  The current study shows that gene transcripts in high stage neuroblastoma tumours are significantly down-regulated compared to those in low stage tumours in the 1p36.22 region. CpG island methylation does not seem to be the mechanism of down-regulation for most of the genes tested, since no methylation was detected in the fragments analyzed. One exception is the CpG island of APITD1. Methylation of this gene is also seen in blood from control individuals and is therefore not believed to participate in tumour development.
  
  
  CONCLUSIONS
  The genes UBE4B, KIF1B, PGD, APITD1, DFFA and PEX14 are down-regulated in high stage NB tumours, a feature that can not be explained by CpG island methylation.
authors.affiliation: Department of Clinical Genetics, Institute for the Health of Women and Children, Göteborg University, Sahlgrenska Univ, Hospital-East, SE-41685 Gothenburg, Sweden. helena.caren@clingen.gu.se <helena.caren@clingen.gu.se>
authors.forename: Helena
authors.initials: H
authors.lastname: Carén
authors.forename: Katarina
authors.initials: K
authors.lastname: Ejeskär
authors.forename: Susanne
authors.initials: S
authors.lastname: Fransson
authors.forename: Luke
authors.initials: L
authors.lastname: Hesson
authors.forename: Farida
authors.initials: F
authors.lastname: Latif
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Sjöberg
authors.forename: Cecilia
authors.initials: C
authors.lastname: Krona
authors.forename: Tommy
authors.initials: T
authors.lastname: Martinsson
mesh_terms: D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger
references.citation: J Natl Cancer Inst. 2004 Aug 18;96(16):1208-19
references.pmid: 15316056
references.citation: Br J Cancer. 2004 Sep 13;91(6):1119-30
references.pmid: 15328517
references.citation: Int J Oncol. 2004 Nov;25(5):1297-302
references.pmid: 15492818
references.citation: Nucleic Acids Res. 1994 Aug 11;22(15):2990-7
references.pmid: 8065911
references.citation: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5520-4
references.pmid: 7777541
references.citation: Hum Mol Genet. 1995 Apr;4(4):535-9
references.pmid: 7633401
references.citation: Cancer Res. 1995 Oct 15;55(20):4664-9
references.pmid: 7553646
references.citation: Cancer Res. 1995 Dec 1;55(23):5681-6
references.pmid: 7585654
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
references.pmid: 8790415
references.citation: Eur J Cancer. 1997 Oct;33(12):1997-2001
references.pmid: 9516841
references.citation: Nucleic Acids Res. 1998 Nov 1;26(21):5009-10
references.pmid: 9776768
references.citation: Nat Genet. 1999 Feb;21(2):163-7
references.pmid: 9988266
references.citation: J Clin Oncol. 1999 Jul;17(7):2264-79
references.pmid: 10561284
references.citation: J Clin Invest. 2000 Feb;105(4):401-7
references.pmid: 10683367
references.citation: Nat Med. 2000 May;6(5):529-35
references.pmid: 10802708
references.citation: Cytogenet Cell Genet. 2000;89(1-2):62-6
references.pmid: 10894940
references.citation: Oncogene. 2000 Aug 31;19(37):4302-7
references.pmid: 10980605
references.citation: Genes Chromosomes Cancer. 2001 Feb;30(2):168-74
references.pmid: 11135433
references.citation: Genes Chromosomes Cancer. 2001 Jun;31(2):172-81
references.pmid: 11319804
references.citation: J Med Genet. 2001 May;38(5):285-303
references.pmid: 11333864
references.citation: Genes Chromosomes Cancer. 2001 Jul;31(3):228-39
references.pmid: 11391793
references.citation: Med Pediatr Oncol. 2001 Jan;36(1):32-6
references.pmid: 11464900
references.citation: Med Pediatr Oncol. 2001 Jan;36(1):37-41
references.pmid: 11464901
references.citation: Med Pediatr Oncol. 2001 Jan;36(1):61-6
references.pmid: 11464908
references.citation: Oncogene. 2001 Nov 8;20(51):7573-7
references.pmid: 11709729
references.citation: Br J Cancer. 2002 Feb 12;86(4):596-604
references.pmid: 11870543
references.citation: Oncogene. 2002 Jun 20;21(27):4345-9
references.pmid: 12082624
references.citation: Oncogene. 2002 Aug 12;21(35):5427-40
references.pmid: 12154405
references.citation: Hum Mol Genet. 2002 Oct 1;11(20):2479-88
references.pmid: 12351584
references.citation: Bioinformatics. 2002 Nov;18(11):1427-31
references.pmid: 12424112
references.citation: Oncogene. 2003 Mar 13;22(10):1580-8
references.pmid: 12629521
references.citation: Oncogene. 2003 Apr 17;22(15):2343-51
references.pmid: 12700669
references.citation: Genes Chromosomes Cancer. 2003 Nov;38(3):226-33
references.pmid: 14506696
references.citation: N Engl J Med. 2003 Nov 20;349(21):2042-54
references.pmid: 14627790