CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected in hepatocellular carcinoma.
High-density single nucleotide polymorphism (SNP) array analysis revealed novel amplification at 1q21 in cell lines derived from hepatocellular carcinomas (HCCs). Fluorescence in situ hybridization and real-time quantitative polymerase chain reaction studies verified amplification at 1q21. An increase in copy number at the region was detected in 32 of the 36 primary HCC tumors (89%). To identify the targets for amplification, we examined 19 HCC cell lines for expression levels of all 26 genes located within the 700-kb amplified region. Five genes were overexpressed in cell lines with amplification at 1q21. Among these, CREB3L4 (cAMP responsive element binding protein 3-like 4), INTS3 (integrator complex subunit 3), and SNAPAP (SNAP-associated protein) were significantly overexpressed in tumors from 18 HCC patients, compared with counterpart nontumorous tissues. The findings suggest that CREB3L4, INTS3, and SNAPAP are probable targets for the amplification mechanism and may therefore be involved, together or separately, in the development or progression of HCCs.
Inagaki
Yoshikazu
Y
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto 602-8566, Japan.
Yasui
Kohichiroh
K
Endo
Mio
M
Nakajima
Tomoaki
T
Zen
Keika
K
Tsuji
Kazuhiro
K
Minami
Masahito
M
Tanaka
Shinji
S
Taniwaki
Masafumi
M
Itoh
Yoshito
Y
Arii
Shigeki
S
Okanoue
Takeshi
T
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017362:Cyclic AMP Response Element-Binding Protein; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured; D033921:Vesicular Transport Proteins / Q000235:genetics*
D050976:Basic-Leucine Zipper Transcription Factors; C448322:CREB3L4 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; C118519:SNAPIN protein, human; D033921:Vesicular Transport Proteins