Inactivation of the RASSF1A in osteosarcoma.
We investigated the expression and mutation of three isoforms of the Ras effector RASSF1 in 10 primary osteosarcomas and 6 osteosarcoma cell lines. RASSF1A was not expressed in 40% (4/10) of the primary osteosarcomas and 83.3% (5/6) of the osteosarcoma cell lines. RASSF1B and RASSF1C expression was absent in 30% (3/10) and 0% (0/10) of primary tumors, and 100% (6/6) and 0% (0/6) of osteosarcoma cell lines, respectively. Treatment of these cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine reactivated the transcription of RASSF1A, but not that of RASSF1B or RASSF1C. No somatic mutations were noted in RASSF1 in either the primary tumors or cell lines. Our data indicate that epigenetic inactivation of RASSF1A by hypermethylation of its promoter region is a frequent event, and may play an important role in the tumorigenesis of osteosarcomas.
Lim
Sungjig
S
Department of Pathology, School of Medicine, Inje University, Sanggye Paik Hospital, Kanazawa, Japan.
Yang
Moon Ho
MH
Park
Jae Hoon
JH
Nojima
Takayuki
T
Hashimoto
Hiroshi
H
Unni
K Krishnan
KK
Park
Yong-Koo
YK
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine