Gastroenterology

Gastroenterology

Volume 119, Issue 2, August 2000, Pages 431-440
Gastroenterology

Liver, Pancreas, and Biliary Tract
Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma,☆☆

https://doi.org/10.1053/gast.2000.9373Get rights and content

Abstract

Background & Aims: Hepatocellular carcinoma (HCC) is highly malignant and prone to recur after surgical treatment. Differentiation between a true relapse of HCC and a second primary tumor is of clinical importance. However, no convenient method is currently available. Methods: Comparative genomic hybridization (CGH) was used to analyze 31 pairs of initial and recurrent HCC samples obtained from patients undergoing 2 consecutive surgeries. The resulting chromosomal aberration profiles were used as genomic fingerprints to determine tumor clonalities and their relationships. Results: Eleven recurrent tumors with high clonal relationship (CR) values (>0.95) were found to be relapsed HCCs, and 11 tumors with CR values close to 0 were found to be second primary HCCs. The other 9 paired samples had inconclusive CR values between 0.95 and 0.4. Two were confirmed by hepatitis B virus integration and X chromosome inactivation analysis to be de novo cancers (CR values, 0.35 and 0.23, respectively). Initial HCCs that subsequently relapsed accumulated more chromosomal aberration events than those that developed de novo HCC (mean, 16.1 ± 4.5 vs. 5.4 ± 4.8 events; P < 0.01). Also, they more frequently showed gains on chromosome arms 3q, 6p, 8q, and 17q and losses on 4q and 16p. Conclusions: CGH is useful for chromosomal aberration study and tumor clonality analysis. More and characteristic genomic changes in the initial HCC suggest that subsequent tumor recurrence is a true relapse.

GASTROENTEROLOGY 2000;119:431-440

Section snippets

Clinical HCC samples

Thirty-one pairs of primary and recurrent HCC from the same patients were collected either from Taichung Veteran General Hospital or National Taiwan University Hospital, Taipei, between 1990 and 1997 (Table 1).Their serologic markers for HBV and HCV infections and α-fetoprotein levels were recorded. After the first curative surgery, the patients were followed up in the outpatient clinic every 1–2 months. Blood chemistry levels, liver function profiles, and α-fetoprotein levels were checked.

Major genomic changes among initial HCC tumors

Thirty-one pairs of initial and recurrent HCC collected from the same patients were analyzed by CGH. Detailed aberration results are shown in Table 1. Among all initial tumors, gain aberrations were detected frequently on chromosome arms 1q (77%), 6p (48%), 8q (45%), 17q (32%), 20q (26%), and 11q (23%). The minimal overlapping regions were at 1q21–23, 6p21–23, 8q24, 17q21, 20q13, and 11q13, respectively. Loss abnormalities were frequently found on chromosome arms 13q (64%), 4q (48%), 8p (39%),

Discussion

CGH is a powerful genetic technique for screening of chromosomal aberrations in a whole genome scale. Informative molecular and cytogenetic data have been obtained since the method was first described in 1992.21 In the present study, we assessed the use of CGH profiles as “tumor genome fingerprints” based on the reasoning that tumor tissues originated from a single clone and that most genomic defects were inherited by its entire progeny. Specifically, we used CGH data as a clonality marker to

Acknowledgements

The authors thank Dr. Kwang-Dong Wuu (National Yang-Ming University) and Prof. Ding-Shinn Chen (National Taiwan University) for their inspiration and valuable comments, and Mei-Chi Lee, Wen-Ping Tseng, Weber Chen, and Eugene Chu for their superior technical assistance and manuscript editing.

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    Address requests for reprints to: Chi-Hung Lin, M.D., Ph.D., Institute of Microbiology and Immunology, National Yang-Ming University, 155, Li-Non Street, Section 2, Taipei, Taiwan 112, Republic of China. e-mail: [email protected]; fax: (886) 2-28212880.

    ☆☆

    Supported by grant NCS 89-2318-B-010-002-M51 from Frontier Medical Genomic Program, National Science Council; grant DD01-86IX-MG-607S from National Health Research Institute Contract Research; grant 89-B-FA22-2-4 from the Program for Promoting Academic Excellence of Universities (to M.-T.H.); and grants from the Yen Tjing Ling Medical Foundation and Chien-Tien Hsu Cancer Research Foundation.

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