Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2.
Artikel i vetenskaplig tidskrift, 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

Författare

Cecilia Krona

Göteborgs universitet

Katarina Ejeskär

Göteborgs universitet

Frida Abel

Göteborgs universitet

Per Kogner

Jill Bjelke

Göteborgs universitet

Elin Björk

Göteborgs universitet

Rose-Marie Sjöberg

Göteborgs universitet

Tommy Martinsson

Göteborgs universitet

Oncogene

0950-9232 (ISSN)

Vol. 22 2343-51

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1038/sj.onc.1206324