A simplified laboratory validated assay for MGMT promoter hypermethylation analysis of glioma specimens from formalin-fixed paraffin-embedded tissue

被引:60
作者
Cankovic, Milena
Mikkelsen, Tom
Rosenblum, Mark L.
Zarbo, Richard J.
机构
[1] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA
[2] Henry Ford Hosp, Dept Neurosurg, Detroit, MI USA
关键词
formalin-fixed tissue; glioblastoma multiforme; methylation-specific PCR; MGMT; promoter hypermethylation; Temozolomide;
D O I
10.1038/labinvest.3700520
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Glioma, and in particular high-grade astrocytoma termed glioblastoma multiforme (GBM), is the most common primary tumor of the brain. Epigenetic silencing of the MGMT (O-6-methylguanine-DNA Methyl transferase) DNA repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with GBM who receive alkylating agents. The methylation status of the MGMT promoter is determined by methylation-specific polymerase chain reaction analysis (MSP). This protocol is often challenging with GBM specimens, because of extensive necrosis and scarcity of malignant cells. The objective of this study was to develop a reliable, clinically validated assay for detection of epigenetic silencing of the MGMT gene using formalin-fixed, paraffin-embedded brain tumor resections and methylation-specific PCR.
引用
收藏
页码:392 / 397
页数:6
相关论文
共 28 条
[1]  
Andersson U, 2004, CLIN NEUROPATHOL, V23, P21
[2]   DNA hypermethylation in tumorigenesis - epigenetics joins genetics [J].
Baylin, SB ;
Herman, JG .
TRENDS IN GENETICS, 2000, 16 (04) :168-174
[3]   Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas [J].
Brell, M ;
Tortosa, A ;
Verger, E ;
Gil, JM ;
Viñolas, N ;
Villá, S ;
Acebes, JJ ;
Caral, L ;
Pujol, T ;
Ferrer, I ;
Ribalta, T ;
Graus, F .
CLINICAL CANCER RESEARCH, 2005, 11 (14) :5167-5174
[4]   Aberrant CpG-island methylation has non-random and tumour-type-specific patterns [J].
Costello, JF ;
Frühwald, MC ;
Smiraglia, DJ ;
Rush, LJ ;
Robertson, GP ;
Gao, X ;
Wright, FA ;
Feramisco, JD ;
Peltomäki, P ;
Lang, JC ;
Schuller, DE ;
Yu, L ;
Bloomfield, CD ;
Caligiuri, MA ;
Yates, A ;
Nishikawa, R ;
Huang, HJS ;
Petrelli, NJ ;
Zhang, XL ;
O'Dorisio, MS ;
Held, WA ;
Cavenee, WK ;
Plass, C .
NATURE GENETICS, 2000, 24 (02) :132-138
[5]  
Esteller M, 1999, CANCER RES, V59, P793
[6]   Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents [J].
Esteller, M ;
Garcia-Foncillas, J ;
Andion, E ;
Goodman, SN ;
Hidalgo, OF ;
Vanaclocha, V ;
Baylin, SB ;
Herman, JG .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (19) :1350-1354
[7]   Generating mutations but providing chemosensitivity:: the role of O6-methylguanine DNA methyltransferase in human cancer [J].
Esteller, M ;
Herman, JG .
ONCOGENE, 2004, 23 (01) :1-8
[8]  
Friedman HS, 2000, CLIN CANCER RES, V6, P2585
[9]   MGMT: Its role in cancer aetiology and cancer therapeutics [J].
Gerson, SL .
NATURE REVIEWS CANCER, 2004, 4 (04) :296-307
[10]  
Gonzalez-Gomez P, 2003, INT J ONCOL, V22, P601