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A cluster of genes located in 1p36 are down-regulated in neuroblastomas with poor prognosis, but not due to CpG island methylation.

Artikel i vetenskaplig tidskrift
Författare Helena Carén
Katarina Ejeskär
Susanne Fransson
Luke Hesson
Farida Latif
Rose-Marie Sjöberg
Cecilia Krona
Tommy Martinsson
Publicerad i Molecular cancer
Volym 4
Nummer/häfte 1
Sidor 10
ISSN 1476-4598
Publiceringsår 2005
Publicerad vid Institutionen för kvinnors och barns hälsa, Avdelningen för pediatrik
Sidor 10
Språk en
Länkar dx.doi.org/10.1186/1476-4598-4-10
Ämnesord Chromosomes, Human, Pair 1, genetics, CpG Islands, genetics, DNA Methylation, Down-Regulation, genetics, Gene Expression Regulation, Neoplastic, Humans, Multigene Family, genetics, Neuroblastoma, genetics, pathology, Prognosis, RNA, Messenger, genetics, Tumor Cells, Cultured
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

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. CONCLUSION: 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.

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