Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2.
Journal article, 2003
Deletion of a part of the short arm of chromosome 1 is one of the most common chromosomal rearrangements observed in neuroblastoma (NBL) tumors and it is associated with a poor prognosis. No NBL tumor suppressor gene has yet been identified in the region. Our shortest region of overlap of deletions, ranging from marker D1S80 to D1S244, was shown to partly overlap a 500 kb region that was homozygously deleted in a NBL cell line. We have screened seven genes known to reside in or very close to this overlap consensus region, UBE4B/UFD2, KIF1B, DFFA, PGD, CORT, PEX14, and ICAT, for coding mutations in NBL tumor DNA. A few deviations from the reference sequences were identified; most interestingly being a splice site mutation that was detected in UBE4B/UFD2 in a stage 3 NBL with a fatal outcome. This mutation was neither present in the patients constitutional DNA nor in any of 192 control chromosomes analysed. Also, the expression of UBE4B/UFD2 was markedly diminished in the high-stage/poor-outcome tumors as compared to the low-stage/favorable-outcome tumors. Overall, the number of amino-acid changes in the genes of the region was low, which shows that mutations in these genes are rare events in NBL development. Given the data presented here, UBE4B/UFD2 stands out as the strongest candidate NBL tumor suppressor gene in the region at this stage.
metabolism
Neoplasm Staging
Genes
Ubiquitin
genetics
metabolism
Prognosis
Gene Expression Regulation
Chromosomes
DNA Mutational Analysis
genetics
pathology
Humans
Treatment Outcome
Multienzyme Complexes
Neoplastic
Pair 1
metabolism
biosynthesis
biosynthesis
Gene Deletion
Loss of Heterozygosity
Human
Neoplasm Proteins
genetics
Amino Acid Substitution
Mutation
genetics
Proteasome Endopeptidase Complex
genetics
DNA
Cysteine Endopeptidases
Tumor Suppressor Proteins
Gene Expression Profiling
Neuroblastoma
Tumor Suppressor
RNA Splice Sites
metabolism
Reverse Transcriptase Polymerase Chain Reaction
Neoplasm
genetics
Author
Cecilia Krona
University of Gothenburg
Katarina Ejeskär
University of Gothenburg
Frida Abel
University of Gothenburg
Per Kogner
Jill Bjelke
University of Gothenburg
Elin Björk
University of Gothenburg
Rose-Marie Sjöberg
University of Gothenburg
Tommy Martinsson
University of Gothenburg
Oncogene
0950-9232 (ISSN)
Vol. 22 15 2343-51Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1038/sj.onc.1206324