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Novel epigenetically deregulated genes in testicular cancer include homeobox genes and SCGB3A1 (HIN-1)
The Journal of pathology, 2006-12, Vol.210 (4), p.441-449
Lind, GE
Skotheim, RI
Fraga, MF
Abeler, VM
Esteller, M
Lothe, RA
2006
Details
Autor(en) / Beteiligte
Lind, GE
Skotheim, RI
Fraga, MF
Abeler, VM
Esteller, M
Lothe, RA
Titel
Novel epigenetically deregulated genes in testicular cancer include homeobox genes and SCGB3A1 (HIN-1)
Ist Teil von
The Journal of pathology, 2006-12, Vol.210 (4), p.441-449
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2006
Link zum Volltext
Quelle
Wiley InterScience Journals
Beschreibungen/Notizen
Testicular germ cell tumours (TGCTs) are classified into two main histological subgroups: seminomas and non‐seminomas. The latter comprise several subtypes: embryonal carcinomas, yolk sac tumours, choriocarcinomas, and teratomas. These embryonal and extra‐embryonal‐like differentiation lineages represent a caricature of early normal development, and inactivation of gene expression through promoter hypermethylation may therefore be of particular importance in germ cell tumourigenesis. The promoter methylation status of ten candidate genes—CDH13, DLX6, EMX2, HOXA9, HOXB5, MSX1, MSX2, RASSF1A, RUNX3, and SCGB3A1 (alias HIN‐1)—was assessed by methylation‐specific PCR in seven intratubular germ cell neoplasias and 55 primary TGCTs. Furthermore, by a discovery‐based global approach, comparing cDNA microarray expression profiles of two germ cell tumour cell lines before and after treatment with the demethylating agent 5‐aza‐2′‐deoxycytidine, a gene list of potentially epigenetic targets was identified, from which CGGBP1, CGRRF1, SMARCC2, SORBS1, and XPA were analysed further. Overall, the non‐seminomas were significantly more often methylated than were seminomas (p < 0.001). The three most frequently methylated genes among this subtype were SCGB3A1 (54%), RASSF1A (29%), and HOXA9 (26%). CDH13 and HOXB5 were methylated at low frequencies (10–15%), and EMX2, MSX1, RUNX3, SORBS1, and XPA only rarely (<10%). In conclusion, this study has identified several novel epigenetically deregulated target genes in TGCT development, including homeobox genes and SCGB3A1, suggesting that epigenetic inactivation of key genes in normal development also has an important role in TGCTs. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.2064
Titel-ID: cdi_crossref_primary_10_1002_path_2064
Format
–
Schlagworte
Carcinoma, Embryonal - genetics
,
Cell Line, Tumor
,
Cytokines - genetics
,
DNA, Neoplasm - genetics
,
Endodermal Sinus Tumor - genetics
,
Epigenesis, Genetic - genetics
,
Gene Expression Regulation, Neoplastic - genetics
,
Genes, Homeobox - genetics
,
germ cell tumour
,
germ cell tumour cell lines
,
HIN-1
,
homeobox genes
,
Homeodomain Proteins - genetics
,
HOXA9
,
Humans
,
Male
,
Methylation
,
Neoplasm Proteins - genetics
,
Neoplasms, Germ Cell and Embryonal - genetics
,
Oligonucleotide Array Sequence Analysis - methods
,
Polymerase Chain Reaction - methods
,
Seminoma - genetics
,
Teratoma - genetics
,
testicular cancer
,
Testicular Neoplasms - genetics
,
Tumor Suppressor Proteins - genetics
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