HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer
- Khawla Al-Kuraya1,
- Hedvika Novotny2,
- Prashant Bavi1,
- Abdul K Siraj1,
- Shahab Uddin1,
- Adnan Ezzat3,
- Nasser Al Sanea4,
- Fouad Al-Dayel5,
- Hadeel Al-Mana5,
- Salwa S Sheikh6,
- Martina Mirlacher2,
- Coya Tapia2,
- Ronald Simon2,
- Guido Sauter2,
- Luigi Terracciano2,
- Luigi Tornillo2
- 1Department of Human Cancer Genomic Research, Research Centre at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- 2Institute of Pathology, Basel University Clinics, 4031 Basel, Switzerland
- 3Department of Medical and Clinical Operations, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- 4Colorectal Unit, Department of Surgery, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- 5Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- 6Saudi Aramco Medical Services Organization, Dhahran, Saudi Arabia
- Correspondence to: Khawla Al-Kuraya Director, Department of Human Cancer Genomic Research, Research Centre, King Faisal Specialist Hospital and Research Center, MBC 98-16, PO Box 3354, Riyadh 11211, KSA; kkuraya{at}kfshrc.edu.sa
- Accepted 22 May 2006
- Published Online First 1 August 2006
Abstract
Aim: Recent studies had suggested substantial molecular differences between tumours from different ethnic groups. In this study, the molecular differences between the incidences of colorectal carcinoma in Saudi and Swiss populations are investigated.
Method: 518 cases of colon cancer tumours (114 from Saudi Arabia and 404 from Switzerland) were analysed in a tissue microarray format. Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C-MYC.
Results: Using FISH, amplifications were mostly low level (gene-to-centromere ratio 2 to 4), which is in contrast with other tumour types with more frequent gene amplifications. The amplifications were particularly frequent for MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological information. Remarkably, there were four tumours exhibiting classic high-level gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR (Swiss 2/355; 0.6%).
Conclusions: Rare high-level amplifications of therapeutic target genes were found in patients with colon cancer. Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies.
- CH, Switzerland
- FISH, Fluorescence in situ hybridisation
- KSA, Kingdom of Saudi Arabia
- TMA, tissue microarray
Footnotes
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Published Online First 2 August 2006
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Funding: This research was funded by the Schweizerischen Arbeitsgemeinschaft für klinische Krebsforschung (SAKK; to CT).
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Competing interests: None declared.
