共 49 条
Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma
被引:37
作者:

Astuti, D
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Morris, M
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Krona, C
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Abel, F
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Gentle, D
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Martinsson, T
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Kogner, P
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Neumann, HPH
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Voutilainen, R
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Eng, C
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Rustin, P
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Latif, F
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机构: Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England

Maher, ER
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h-index: 0
机构:
Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England
机构:
[1] Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England
[2] Univ Birmingham, Sch Med, Canc Res UK Renal Mol Oncol Res Grp, Birmingham B15 2TT, W Midlands, England
[3] Gothenburg Univ, Sahlgrenska Univ Hosp Ostra, Dept Clin Genet, S-41685 Gothenburg, Sweden
[4] Karolinska Hosp, Karolinska Inst, Dept Woman & Child Hlth, Childhood Canc Res Unit, S-17176 Stockholm, Sweden
[5] Med Univ Klin, D-79106 Freiburg, Germany
[6] Kuopio Univ Hosp, Dept Paediat, FIN-70211 Kuopio, Finland
[7] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland
[8] Ohio State Univ, Dept Internal Med, Div Human Genet,Comprehens Canc Ctr, Clin Canc Genet Program, Columbus, OH 43210 USA
[9] Ohio State Univ, Dept Internal Med, Div Human Genet,Comprehens Canc Ctr, Human Canc Genet Program, Columbus, OH 43210 USA
[10] Hop Necker Enfants Malad, INSERM, U393, F-75015 Paris, France
关键词:
SDHB;
methylaton;
neuroblastoma;
phaeochromocytoma;
D O I:
10.1038/sj.bjc.6602202
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Germline mutations in the succinate dehydrogenase (SDH) (mitochondrial respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head and neck paraganglioma and phaeochromocytoma. Previously, we did not identify somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a region of frequent loss of heterozygosity (LOH) in neuroblastoma as well. Hence, to evaluate SDHB as a candidate neuroblastoma tumour suppressor gene (TSG) we performed mutation analysis in 46 primary neuroblastomas by direct sequencing, but did not identify germline or somatic SDHB mutations. As TSGs such as RASSFIA are frequently inactivated by promoter region hypermethylation, we designed a methylation-sensitive PCR-based assay to detect SDHB promoter region methylation. In 21% of primary neuroblastomas and 32% of phaeochromocytomas (32%) methylated (and unmethylated) alleles were detected. Although promoter region methylation was also detected in two neuroblastoma cell lines, this was not associated with silencing of SDHB expression, and treatment with a demethylating agent (5-azacytidine) did not increase SDH activity. These findings suggest that although germline SDHB mutations are an important cause of phaeochromocytoma susceptibility, somatic inactivation of SDHB does not have a major role in sporadic neural crest tumours and SDHB is not the target of 1p36 allele loss in neuroblastoma and phaeochromocytoma.
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页码:1835 / 1841
页数:7
相关论文
共 49 条
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Sjöberg, RM
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Sahlgrens Univ Hosp E, Univ Gothenburg, Dept Clin Genet, S-41685 Gothenburg, Sweden Sahlgrens Univ Hosp E, Univ Gothenburg, Dept Clin Genet, S-41685 Gothenburg, Sweden

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Sahlgrens Univ Hosp E, Univ Gothenburg, Dept Clin Genet, S-41685 Gothenburg, Sweden Sahlgrens Univ Hosp E, Univ Gothenburg, Dept Clin Genet, S-41685 Gothenburg, Sweden

Martinsson, T
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