title: Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas.
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.
authors.forename: Limei
authors.initials: L
authors.lastname: Ouyang
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Cheol-Keun
authors.initials: CK
authors.lastname: Park
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Yujian
authors.initials: Y
authors.lastname: Shi
authors.forename: Zhuolin
authors.initials: Z
authors.lastname: Gong
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Guangbiao
authors.initials: G
authors.lastname: Wang
authors.forename: Huiling
authors.initials: H
authors.lastname: Fu
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. jkimsmc@skku.edu.
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D017809:Fatal Outcome; D005787:Gene Frequency / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D022821:RNA Splice Sites / Q000235:genetics; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics
chemical_list: D022821:RNA Splice Sites