Frequent loss of chromosome 3p and hypermethylation of RASSF1A in cholangiocarcinoma.
OBJECTIVE
Cholangiocarcinoma comprises 5-20% of all primary malignant tumors of the liver. However, the lack of information about the genetic basis of cholangiocarcinoma has impeded characterization and understanding of its biological behavior.


METHODS
In this study, genome-wide aberrations in 13 cases of cholangiocarcinoma were examined by the molecular cytogenetic technique, comparative genomic hybridization.


RESULTS
Frequent gains of 1q, 3q, 8q, 15q and 17q, and common losses on 3p, 4q, 6q, 9p, 17p and 18q were found. The finding of common chromosome 3p loss (approximately 40%) with a minimal deleted region of 3p13-p21 has prompted our further investigation on the tumor suppressor gene RASSF1A, located at 3p21.3. Using bisulphite modification followed by methyl-specific PCR, a high incidence of methylated RASSF1A promoter region was detected in our current series (9/13 cases; 69%). Further expression analysis on the nine cases with promoter hypermethylation indicated much reduced RASSF1A expression compared to normal livers.


CONCLUSIONS
Our current molecular cytogenetic investigation on primary cholangiocarcinoma provided overall karyotypic information and represents the first report on the methylation status of RASSF1A in cholangiocarcinoma. The high incidence of 3p loss and RASSF1A promoter hypermethylation detected may have implications for this tumor suppressor gene in the malignant progression of cholangiocarcinoma.
Wong
Nathalie
N
Department of Clinical Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
Li
Libby
L
Tsang
Kareena
K
Lai
Paul B-S
PB
To
Ka-Fai
KF
Johnson
Philip J
PJ
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins