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Evolution of genetic abnormalities in hepatocellular carcinomas demonstrated by DNA fingerprinting
Author(s) -
Sirivatanauksorn Yongyut,
Sirivatanauksorn Vorapan,
Bhattacharya Satyajit,
Davidson Brian R.,
Dhillon Amar P.,
Kakkar Ajay K.,
Williamson Robin C. N.,
Lemoine Nicholas R.
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199911)189:3<344::aid-path430>3.0.co;2-g
Subject(s) - hccs , microdissection , hepatocellular carcinoma , polymerase chain reaction , biology , laser capture microdissection , pathology , dna , microbiology and biotechnology , cancer research , gene , genetics , medicine , gene expression
Hepatocellular carcinomas (HCC) often contain subpopulations of cells showing heterogeneous differentiation within each tumour. The majority of HCCs first appear as well‐differentiated lesions and proliferate with gradual dedifferentiation. The present study was designed to investigate the clonal diversity which is seen with progression in neoplasms. The degree of genomic heterogeneity of HCC nodules was assessed using the arbitrarily primed‐polymerase chain reaction technique. Two or more sectors of 31 HCC nodules were needle‐microdissected and amplified with two different arbitrary primers in appropriate conditions. In every HCC less than 6 mm in diameter ( n =18, range 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 DNA fingerprint. These results suggest that a process of clonal evolution occurs 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 clonality in HCCs, including borderline cases, are made possible by the combination of these novel techniques. Copyright © 1999 John Wiley & Sons, Ltd.