Journal Article

Novel targets for the 18p11.3 amplification frequently observed in esophageal squamous cell carcinomas

Koichi Nakakuki, Issei Imoto, Atiphan Pimkhaokham, Yoji Fukuda, Yutaka Shimada, Masayuki Imamura, Teruo Amagasa and Johji Inazawa

in Carcinogenesis

Volume 23, issue 1, pages 19-24
Published in print January 2002 | ISSN: 0143-3334
Published online January 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.1.19
Novel targets for the 18p11.3 amplification frequently observed in esophageal squamous cell carcinomas

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Amplification of DNA in certain chromosomal regions, with consequent over-expression of specific genes within these amplicons, plays a crucial role in the development and progression of human cancer. Since our previous comparative genomic hybridization (CGH) study revealed frequent amplifications at 18p in esophageal squamous cell carcinomas (ESC) cell lines, we focused on the identification of genetic target(s) within the 18p amplicon. In four cell lines having remarkable copy-number amplification with homogeneously staining region (HSR) pattern by fluorescence in situ hybridization (FISH), the smallest common region of overlapping covered ~3.5 Mb at 18p11.3. We screened 29 ESC cell lines to discern amplifications and expression levels of 14 known genes and 21 uncharacterized transcripts within the amplicon. Only four known genes, YES1, TYMS, HEC and TGIF showed amplification and consequent over-expression. These genes were amplified in several of primary ESCs. Moreover, resistance to transforming growth factorβ (TGFβ)-induced growth inhibition was enhanced in four cell lines with amplification and expression of TGIF, which encodes the repressor for TGFβ-activated transcription, appears to be involved in the progression of ESC. Taken together, these results suggest that YES1, TYMS, HEC and TGIF are likely to be candidate targets for 18p11.3 amplification and be associated with esophageal tumorigenesis.

Keywords: BACs, bacterial artificial chromosomes; CGH, comparative genomic hybridization; ESC, esophageal squamous cell carcinomas; 5FU, 5-fluorouracil; SCC, squamous cell carcinomas; TGFβ, transforming growth factorβ; TS, thymidylate synthase.

Journal Article.  4282 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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