Journal Article

Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

Ouyang, Limei, Wang, Guangbiao, Fu, Huiling, Lim, Ho Yeong, Li, Yingrui, Mao, Mao, Gong, Zhuolin, Zhao, Yonggang, Lee, Jeeyun, Zheng, Hancheng, Park, Cheol-Keun, Shi, Yujian, Kim, Jhingook

2014

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Adult / Analysis / Biomedical and Life Sciences / Biomedicine / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - pathology / Care and treatment / Comparative analysis / Disease Progression / DNA Copy Number Variations - genetics / DNA Mutational Analysis / DNA sequencing / Fatal Outcome / Functional and structural genomics / Gene Expression / Gene Frequency - genetics / Genetic aspects / Genome, Human - genetics / Hepatitis / Human Genetics / Humans / Liver / Liver cancer / Liver cirrhosis / Liver Neoplasms - genetics / Liver Neoplasms - pathology / Male / Medical research / Metastasis / Microarrays / Middle Aged / Mutation / Mutation - genetics / Neoplasm Metastasis / Nucleotide sequencing / Research Article / RNA Splice Sites - genetics / Sequence Analysis, DNA / Signal Transduction - genetics