Genetic and epigenetic changes in the common 1p36 deletion in neuroblastoma tumours

• Published in: British journal of cancer 2007-11, Vol.97 (10), p.1416-1424
• Main Authors: Carén, H, Fransson, S, Ejeskär, K, Kogner, P, Martinsson, T
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - drug effects; Adaptor Proteins, Signal Transducing - genetics; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Line, Tumor; Chromosome Deletion; Chromosomes; Chromosomes, Human, Pair 1 - genetics; Class I Phosphatidylinositol 3-Kinases; Decitabine; DNA Methylation; DNA Mutational Analysis; DNA, Neoplasm - genetics; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - genetics; Drug Resistance; Epidemiology; Epigenetics; Exons; Genetic Variation; Genetics and Genomics; Histones - metabolism; Humans; Hydroxamic Acids - pharmacology; Medical and Health Sciences; Medicin och hälsovetenskap; Molecular Medicine; Mutation; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - pathology; Oncology; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - genetics; Polymorphism, Genetic - genetics; Retinol-Binding Proteins, Cellular - drug effects; Retinol-Binding Proteins, Cellular - genetics; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription, Genetic - drug effects; Transcription, Genetic - genetics; Tumor Suppressor Proteins; Up-Regulation - drug effects
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604032

Chromosome 1p is frequently deleted in neuroblastoma (NB) tumours. The commonly deleted region has been narrowed down by loss of heterozygosity studies undertaken by different groups. Based on earlier mapping data, we have focused on a region on 1p36 (chr1: 7 765 595–11 019 814) and performed an analysis of 30 genes by exploring features such as epigenetic regulation, that is DNA methylation and histone deacetylation, mutations at the DNA level and mRNA expression. Treatment of NB cell lines with the histone deacetylase inhibitor trichostatin A led to increased gene transcription of four of the 30 genes, ERRFI1 (MIG-6) , PIK3CD , RBP7 (CRBPIV) and CASZ1 , indicating that these genes could be affected by epigenetic downregulation in NBs. Two patients with nonsynonymous mutations in the PIK3CD gene were detected. One patient harboured three variations in the same exon, and p.R188W. The other patient had the variation p.M655I. In addition, synonymous variations and one variation in an intronic sequence were also found. The mRNA expression of this gene is downregulated in unfavourable, compared to favourable, NBs. One nonsynonymous mutation was also identified in the ERRFI1 gene, p.N343S, and one synonymous. None of the variations above were found in healthy control individuals. In conclusion, of the 30 genes analysed, the PIK3CD gene stands out as one of the most interesting for further studies of NB development and progression.