Abnormalities of chromosome 17 in oesophageal cancer

Oesophageal cancer is the most common malignancy encountered in South African males, especially in the Eastern Cape and surrounding region of South Africa. There are a number of risk factors and predisposing conditions that have been implicated in the aetiology of the disease. The tylosis oesophageal cancer (TOC) gene, localised to a small region on chromosome 17q25, has been shown to be associated with oesophageal squamous cell carcinoma.

To investigate loss of heterozygosity (LOH) and microsatellite instability (MSI) in the region of the TOC locus.

In 74 oesophagectomy specimens for squamous cell carcinoma, microsatellite PCR was performed using five fluorescently labelled TOC markers. The PCR products were analysed and the data correlated with clinicopathological findings.

LOH ranged from 25% to 60%. LOH for the individual markers was as follows: D17S1839, 25%; D17S1864, 36%; D17S1817, 38%; D17S785, 47.8%; and D17S579, 60%. MSI ranged from 4.1% to 6.8% for the five loci in the 17q region. MSI was 4.1% for the markers D17S579, D17S785 and D17S1817. Marker D17S1864 showed MSI to occur in 4 cases (5.4%) and marker D17S1839 in 5 cases (6.8%).

No significant relationship between genetic and clinical parameters was observed; however, aberrations in poorly differentiated tumours were high for markers D17S579 and D17S1864 (25% and 37%, respectively), indicating that these markers may have an underlying role in the molecular pathogenesis of oesophageal squamous cell carcinoma. In addition, 63% of patients who died showed LOH for the markers D17S579, D17S1864 and D17S1817.