QUANTITATION OF THE ALLELIC IMBALANCE PROVIDES EVIDENCE ON TUMOR HETEROGENEITY - A HYPOTHESIS

The observation of loss of heterozygosity (LOH) in tumours represents a useful clue to the presence of tumour suppressor genes (TSGs). Howev er, analysis of this phenomenon is often complicated by tumour heterog eneity and the presence of DNA from adjacent normal tissues. The prese nt study suggests a quantitative approach for measurement of LOH which may help to distinguish between these possibilities and to provide cl ues for the heterogeneous process of tumour progression. We applied th is methodology to a laryngeal tumour with LOH at markers D9S171, D9S15 7, D8S87 and THRA1 and found that LOH at D9S171 is the commonest aberr ation among the tumour cells, while LOH at the THRA1 marker is present in only a small subset of the tumour cells. It is likely that LOH at D9S171 occurs early in tumour development while LOH at the rest of the markers tested occurred later resulting in the generation of heteroge neous cell populations.