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Open Access Research article

Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

Limei Ouyang1, Jeeyun Lee2, Cheol-Keun Park3, Mao Mao4, Yujian Shi1, Zhuolin Gong1, Hancheng Zheng1, Yingrui Li1, Yonggang Zhao1, Guangbiao Wang1, Huiling Fu1, Jhingook Kim5* and Ho Yeong Lim2*

Author Affiliations

1 BGI-Shenzhen, Beishan Industrial Zone, Beishan Road, Shenzhen, Yantian 518083, People’s Republic of China

2 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea

3 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea

4 Oncology Research Unit, Pfizer Inc., San Diego CA 92121, USA

5 Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea

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BMC Medical Genomics 2014, 7:2  doi:10.1186/1755-8794-7-2

Published: 9 January 2014

Abstract

Background

To gain biological insights into lung metastases from hepatocellular carcinoma (HCC), we compared the whole-genome sequencing profiles of primary HCC and paired lung metastases.

Methods

We used whole-genome sequencing at 33X-43X coverage to profile somatic mutations in primary HCC (HBV+) and metachronous lung metastases (> 2 years interval).

Results

In total, 5,027-13,961 and 5,275-12,624 somatic single-nucleotide variants (SNVs) were detected in primary HCC and lung metastases, respectively. Generally, 38.88-78.49% of SNVs detected in metastases were present in primary tumors. We identified 65–221 structural variations (SVs) in primary tumors and 60–232 SVs in metastases. Comparison of these SVs shows very similar and largely overlapped mutated segments between primary and metastatic tumors. Copy number alterations between primary and metastatic pairs were also found to be closely related. Together, these preservations in genomic profiles from liver primary tumors to metachronous lung metastases indicate that the genomic features during tumorigenesis may be retained during metastasis.

Conclusions

We found very similar genomic alterations between primary and metastatic tumors, with a few mutations found specifically in lung metastases, which may explain the clinical observation that both primary and metastatic tumors are usually sensitive or resistant to the same systemic treatments.

Keywords:
Cancer; Hepatocellular carcinomas (HCC); Lung metastasis; Somatic; Next-generation sequencing (NGS)