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| Status |
Public on Feb 09, 2011 |
| Title |
NDRG2 transcriptional inactivation is involved in tumoral progression and worse clinical outcome of oligodendroglial tumors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Purpose: The most clearly established genetic hallmark in oligodendroglial tumors (OTs) is the combined loss of 1p/19q, a molecular alteration characteristic of tumors responding to therapy. Markers of tumoral progression have not yet been studied.
Experimental Design: Novel markers of tumoral progression in OTs were sought through gene expression profiling analysis.
Results: Unsupervised hierarchical cluster analysis classified OTs into two main groups associated with tumoral grade, independent of histological subtype and 1p/19q status. Differential gene expression analysis between low- and high-grade OTs revealed that only cell cycle-related genes were significantly upregulated in high-grade OTs. Among the deregulated genes, NDRG2 downregulation was detected in high-grade OTs with combined loss of 1p/19q. Expression analysis revealed low transcript levels of NDRG2 relative to non-tumoral brain tissue in 45% (9/20) of high-grade OTs. Furthermore, the low transcript levels of NDRG2 were significantly associated with a worse clinical outcome in patients. Transcript levels of NDRG2 were associated with promoter hypermethylation, which was detected in 38.4% (10/26) of high-grade OTs. The treatment of glioma cell lines T98 and LN18 with demethylating agents increased the mRNA expression levels of NDRG2 relative to the control cell line. Additionally, cell proliferation was significantly reduced and cell cycle was arrested in G1 phase after treatment with demethylating agents.
Conclusions: Taken together, our results suggest that NDRG2 is a candidate tumor suppressor gene in OTs whose inactivation could be involved in tumoral progression and worse patient survival.
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| Overall design |
The microarray study involved 28 glioma samples including oligodendrogliomas and oligoastrocytomas WHO grade II and III. Six non-tumoral brain tissues were used as controls, two of which were purchased from Stratagene (La Jolla, CA) and Clontech (Mountain View, CA). RNAs from several cell lines (Universal Human RNA, Stratagene, La Jolla, CA) was used as a standard reference in all hybridizations
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| Contributor(s) |
Ruano Y, Rodriguez de Lope A, Ribalta T, Fiaño C, García J, Campos-Martín Y, Pérez-Magán E, Ferrara P, Hernández-Moneo J, Mollejo M, Meléndez B |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Feb 02, 2011 |
| Last update date |
Sep 01, 2015 |
| Contact name |
Barbara Melendez |
| E-mail(s) |
bmelendez@sescam.jccm.es
|
| Phone |
34 925 269 245
|
| Organization name |
HOSPITAL VIRGEN DE LA SALUD
|
| Department |
UNIDAD DE INVESTIGACION DE PATOLOGIA MOLECULAR
|
| Lab |
GRUPO DE ESTUDIO DE TUMORES DEL SISTEMA NERVIOSO CENTRAL
|
| Street address |
AVDA. BARBER 30
|
| City |
TOLEDO |
| ZIP/Postal code |
45004 |
| Country |
Spain |
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| Platforms (1) |
| GPL6848 |
Agilent-012391 Whole Human Genome Oligo Microarray G4112A (Probe Name version) |
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| Samples (28)
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| GSM556666 |
Brain_Oligodendroglioma-gradeII_940 |
| GSM637565 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_886 |
| GSM637566 |
Brain_Oligoastrocytoma-gradeII_1967 |
| GSM637569 |
Brain_Oligoastrocytoma-gradeII_1971 |
| GSM637570 |
Brain_Oligoastrocytoma-gradeII_1976 |
| GSM637571 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_1018 |
| GSM637572 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_1056 |
| GSM638868 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_1079 |
| GSM638913 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_1632 |
| GSM638926 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_1881 |
| GSM638927 |
Brain_Anaplastic-Oligoastrocytoma-gradeIII_1882 |
| GSM638928 |
Brain_Oligodendroglioma-gradeII_901 |
| GSM638941 |
Brain_Oligodendroglioma-gradeII_902 |
| GSM638954 |
Brain_Oligodendroglioma-gradeII_903 |
| GSM639455 |
Brain_Oligodendroglioma-gradeII_938 |
| GSM639456 |
Brain_Oligodendroglioma-gradeII_947 |
| GSM639457 |
Brain_Oligodendroglioma-gradeII_936 |
| GSM639458 |
Brain_Oligodendroglioma-gradeII_935 |
| GSM639459 |
Brain_Oligodendroglioma-gradeII_937 |
| GSM639460 |
Brain_Oligodendroglioma-gradeII_939 |
| GSM639461 |
Brain_Oligodendroglioma-gradeII_1768 |
| GSM639462 |
Brain_Oligodendroglioma-gradeII_1015 |
| GSM645009 |
Brain_Anaplastic-Oligodendroglioma-gradeIII_1014 |
| GSM645010 |
Brain_Anaplastic-Oligodendroglioma-gradeIII_1518 |
| GSM645011 |
Brain_Anaplastic-Oligodendroglioma-gradeIII_1763 |
| GSM645012 |
Brain_Anaplastic-Oligodendroglioma-gradeIII_1765 |
| GSM645013 |
Brain_Anaplastic-Oligodendroglioma-gradeIII_1770 |
| GSM645014 |
Brain_Anaplastic-Oligodendroglioma-gradeIII_1017 |
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| Relations |
| BioProject |
PRJNA137661 |
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