Genomic heterogeneity in synchronous hepatocellular carcinomas

Area of Science:

• Hepatobiliary surgery
• Surgical oncology
• Genomics

Background:

• Hepatocellular carcinoma (HCC) in cirrhosis often presents as multifocal disease.
• The clonal origin of multifocal HCC (monoclonal vs. polyclonal) remains unclear.
• It is not established whether smaller synchronous HCC nodules are intrahepatic metastases or de novo primary tumors.

Purpose of the Study:

• To evaluate the extent of genomic heterogeneity within synchronous HCCs in cirrhotic patients.
• To investigate the relationship between genomic patterns and tumor origin in multifocal HCC.

Main Methods:

• Arbitrarily primed polymerase chain reaction (AP-PCR) was employed.
• DNA fingerprints of HCCs and regenerative nodules (RNs) from cirrhotic explant livers were compared.
• Genomic analysis was performed on microdissected tumor nodules.

Main Results:

• Significant polymorphic genomic heterogeneity was observed in 54 HCCs and 31 RNs.
• Even adjacent satellite nodules within the same liver segment exhibited distinct genomic profiles.
• This genomic diversity indicates independent origins for synchronous nodules.

Conclusions:

• Genomic heterogeneity in synchronous HCCs may contribute to poor patient outcomes post-resection.
• Findings suggest smaller HCC nodules are likely de novo lesions, not metastases.
• Current liver resection paradigms for HCC may need reevaluation if smaller tumors arise independently.