Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

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• 作者：Limei Ouyang (1)
  Jeeyun Lee (2)
  Cheol-Keun Park (3)
  Mao Mao (4)
  Yujian Shi (1)
  Zhuolin Gong (1)
  Hancheng Zheng (1)
  Yingrui Li (1)
  Yonggang Zhao (1)
  Guangbiao Wang (1)
  Huiling Fu (1)
  Jhingook Kim (5)
  Ho Yeong Lim (2)
  
• 关键词：Cancer ; Hepatocellular carcinomas (HCC) ; Lung metastasis ; Somatic ; Next ; generation sequencing (NGS)
• 刊名：BMC Medical Genomics
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：1,191 KB
• 作者单位：Limei Ouyang (1)
  Jeeyun Lee (2)
  Cheol-Keun Park (3)
  Mao Mao (4)
  Yujian Shi (1)
  Zhuolin Gong (1)
  Hancheng Zheng (1)
  Yingrui Li (1)
  Yonggang Zhao (1)
  Guangbiao Wang (1)
  Huiling Fu (1)
  Jhingook Kim (5)
  Ho Yeong Lim (2)
  
  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
  
• ISSN：1755-8794

文摘

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 65-21 structural variations (SVs) in primary tumors and 60-32 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.