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. 1999 Nov;45(5):761–765. doi: 10.1136/gut.45.5.761

Genomic heterogeneity in synchronous hepatocellular carcinomas

Y Sirivatanauksorn 1, V Sirivatanauksorn 1, S Bhattacharya 1, B Davidson 1, A Dhillon 1, A Kakkar 1, R Williamson 1, N Lemoine 1
PMCID: PMC1727708  PMID: 10517917

Abstract

BACKGROUND—Hepatocellular carcinoma (HCC) arising in cirrhosis is frequently multifocal. Whether HCC develops monoclonally or multiclonally is an unresolved question. Of the multiple tumour nodules present in many patients, it has not been established whether the smaller lesions represent intrahepatic metastases or de novo cancers.
AIMS—To assess the degree of genomic heterogeneity in synchronous HCCs in cirrhosis.
METHODS—The arbitrarily primed polymerase chain reaction technique was utilised to compare the DNA fingerprint of HCCs and regenerative nodules (RNs) removed from cirrhotic explant livers.
RESULTS—Polymorphic genomic heterogeneity was noted in 54 HCCs and 31 RNs microdissected. Even satellite nodules in close proximity within the same segment of the liver were found to have distinct genomic patterns.
CONCLUSION—Such genomic heterogeneity in synchronous HCCs may explain poor patient survival after surgical resection. If the smaller tumours are de novo lesions rather than metastases (as these data suggest), then current concepts regarding liver resection as a curative treatment modality for HCC may require reassessment.


Keywords: hepatocellular carcinoma; regenerative nodule; cirrhosis; DNA fingerprint; arbitrarily primed polymerase chain reaction; genomic heterogeneity

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Figure 1  .

Figure 1  

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AP-PCR fingerprint patterns of fresh frozen and formalin fixed, paraffin wax embedded blocks of two segments (A and B) of non-cirrhotic liver from a single patient. Identical profiles were observed on amplification of DNA from microdissected samples at different levels of the frozen blocks (F1 and F2) and paraffin wax blocks (P1 and P2). Similar results were obtained on amplification of various concentrations (a: 50 ng; b: 100 ng; c: 200 ng; d: 400 ng) of template DNA from each of the paraffin wax blocks.

Figure 2  .

Figure 2  

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Typical genomic AP-PCR fingerprinting of synchronous hepatocellular carcinoma (HCC) and regenerative nodules (RNs) in the cirrhotic liver of one patient. Autoradiograms of polyacrylamide gel electrophoresis of 33P-labelled DNA fragments amplified by arbitrary primers, AR3 (A) and ZF3 (B), showed high polymorphism between different nodules. N, R1-R3, and T1-T7 represent paired PCR reaction samples from non-tumour tissue, three different RNs, and seven different HCC nodules, respectively. Size of bands (in base pairs) is indicated on the right.

Figure 3  .

Figure 3  

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AP-PCR analysis of primary and satellite hepatocellular carcinoma (HCC) nodules. Autoradiograms of polyacrylamide gel electrophoresis of 33P-labelled DNA fragments amplified by AP-PCR. Genomic DNA from each sample was amplified with the AR3 (A) and ZF3 (B) arbitrary primers. S1, S2, and S3 represent the three different sectors in the same primary HCC nodule of patient Sc. N, 1-3, and A-E represent non-tumour tissue, three different sectors of primary, and five satellite HCC lesions of patient Go, respectively. Size of bands (in base pairs) is indicated on the right.

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