Clonal origin of multifocal hepatocellular carcinoma

Kurt B. Hodges, Oscar W. Cummings, Romil Saxena, Mingsheng Wang, Shaobo Zhang, Antonio Lopez-Beltran, Rodolfo Montironi, Hammam Nour, Liang Cheng

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

BACKGROUND: Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain. METHODS: The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations. RESULTS: Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors. CONCLUSIONS: The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin.

Original languageEnglish (US)
Pages (from-to)4078-4085
Number of pages8
JournalCancer
Volume116
Issue number17
DOIs
StatePublished - Sep 1 2010

Keywords

  • Clonality
  • Liver
  • Loss of heterozygosity
  • Multifocal
  • TP53 mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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