Deletion and aberrant CpG island methylation of Caspase 8 gene in medulloblastoma.
Aberrant methylation of promoter CpG islands in human genes is an alternative genetic inactivation mechanism that contributes to the development of human tumors. Nevertheless, few studies have analyzed methylation in medulloblastomas. We determined the frequency of aberrant CpG island methylation for Caspase 8 (CASP8) in a group of 24 medulloblastomas arising in 8 adult and 16 pediatric patients. Complete methylation of CASP8 was found in 15 tumors (62%) and one case displayed hemimethylation. Three samples amplified neither of the two primer sets for methylated or unmethylated alleles, suggesting that genomic deletion occurred in the 5' flanking region of CASP8. Our findings suggest that methylation commonly contributes to CASP8 silencing in medulloblastomas and that homozygous deletion or severe sequence changes involving the promoter region may be another mechanism leading to CASP8 inactivation in this neoplasm.
Laboratorio de Oncogenética Molecular y Epigenética del Cáncer, Departamento de C. Experimental, Unidad de Investigación, Hospital Universitario La Paz, Paseo Castellana 261, 28046 Madrid, Spain.
Pilar
P
Gonzalez-Gomez
M Josefa
MJ
Bello
M Mar
MM
Inda
M Eva
ME
Alonso
Dolores
D
Arjona
Cinthia
C
Amiñoso
Isabel
I
Lopez-Marin
Jose M
JM
de Campos
Jose L
JL
Sarasa
Javier S
JS
Castresana
Juan A
JA
Rey
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006720:Homozygote; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D017931:DNA Primers; D004247:DNA; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases