J Korean Med Sci.  2004 Oct;19(5):682-687. 10.3346/jkms.2004.19.5.682.

Genetic Alterations in Intrahepatic Cholangiocarcinoma as revealed by Degenerate Oligonucleotide Primed PCR-Comparative Genomic Hybridization

• Lee JY
• Park YN
• Uhm KO
• Park SY
• Park SH

• KMID: 1733509
• DOI: http://doi.org/10.3346/jkms.2004.19.5.682

Abstract

Intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm of the biliary epithelium, is usually fatal because of difficulty in early diagnosis and lack of availability of effective therapy. The genetic mechanisms involved in the development of ICC are not well understood and only a few cytogenetic studies of ICC have been published. Recently, technique of degenerate oligonucleotide primed (DOP)-PCR comparative genomic hybridization (CGH) permits genetic imbalances screening of the entire genome using only small amounts of tumor DNA. In this study chromosomal aberrations in 33 Korean ICC were investigated by DOP-PCR CGH. The common sites of copy number increases were 20q (67%), 17 (61%), 11q11-q13 (42%), 8p12-qter (39%), 18p (39%), 15q22-qter (36%), 16p (36%), 6p21 (30%), 3q25-qter (27%), 1q41-qter (24%), and 5p14-q11.2 (24%). DNA amplification was identified in 16 carcinomas (48%). The frequent sites of amplification were 20q, 17p, 17q23-qter, and 7p. The most frequent sites of copy number decreases were 1p32-pter (21%) and 4q (21%). The recurrent chromosomal aberrations identified in this study provide candidate regions involved in the tumorigenesis and progression of ICC.

Keyword

Cholangiocarcinoma, Chromosome Aberrations, Comparative Genomic Hybridization; Polymerase Chain Reaction

MeSH Terms

Adult
Aged
Bile Duct Neoplasms/*genetics
*Bile Ducts, Intrahepatic
Cholangiocarcinoma/*genetics
*Chromosome Aberrations
DNA Primers
Female
Gene Dosage
Humans
Male
Middle Aged
Nucleic Acid Hybridization/methods
Oligonucleotides
Polymerase Chain Reaction/*methods
Research Support, Non-U.S. Gov't

Figure

• 

  Fig. 1 Summary for gains and losses of chromosomal regions in 33 cholangiocarcinomas. Gains are shown on the right side of the chromosome ideograms and losses on the left. Each line illustrates the affected region of the chromosome in a single tumor sample. Thick lines represent high-level amplifications.

• 

  Fig. 2 Examples of the CGH profiles of chromosomal aberrations in ICC. Red and green lines represent thresholds for chromosomal losses (0.75) and gains (1.25), respectively. (A) Gain of 3q26-qter was detected, (B) Deletion of 4p15-qter was observed, (C) Overrepresentation of 8q22-qter with high amplification of 8q24 was found, (D) Gain of 11p11-q13 was detected, (E) Gain of 18p was observed, (F) Gain of 20q was found. *n=number of chromosomes evaluated.

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