Evolution of genetic abnormalities in hepatocellular carcinomas demonstrated by DNA fingerprinting

Hepatocellular carcinomas (HCC) often contain subpopulations of cells showi ng heterogeneous differentiation within each tumour. The majority of HCCs f irst appear as well-differentiated lesions and proliferate with gradual ded ifferentiation. The present study was designed to investigate the clonal di versity which is seen with progression in neoplasms. The degree of genomic heterogeneity of WCC nodules was assessed using the arbitrarily primed-poly merase chain reaction technique. Two or more sectors of 31 HCC nodules were needle-microdissected and amplified with two different arbitrary primers i n appropriate conditions. In every HCC less than 6 mm in diameter (n=18, ra nge 3-6 mm, mean diameter 4.7 mm), all sectors of each of these lesions had the same DNA fingerprint. All HCC nodules greater than 6 mm diameter (n=13 , range 7-30 mm, mean diameter 15.4 mm) showed distinct DNA fingerprints in each sector sampled (p<0.05, compared with size less than 6 mm in diameter ). When synchronous HCCs were present, no two tumour nodules had the same D NA fingerprint. These results suggest that a process of clonal evolution oc curs in expanding HCC, with neoplasms more than 6 mm in diameter developing as multiple clones, The advent of laser capture microdissection technology makes such analysis much more rapid and easily applied. Studies of clonali ty in HCCs, including borderline cases, are made possible by the combinatio n of these novel techniques. Copyright (C) 1999 John Wiley & Sons, Ltd.