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Cited by 72Genomic variations and chromosomal abnormalitiesCancer Genomics and DiagnosticsGenomics and Phylogenetic Studies

Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2

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Zhou, Bo, Ho, Steve S, Greer, Stephanie U, Spies, Noah, Bell, John M, Zhang, Xianglong, Zhu, Xiaowei, Arthur, Joseph G +10 more·2019·Nucleic Acids Research
DOI 10.1093/nar/gkz169PMC PMC6486628

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Abstract

HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order genomic structural features are largely unknown. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line's genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of genome characteristics in HepG2: copy numbers of chromosomal segments at high resolution, SNVs and Indels (corrected for aneuploidy), regions with loss of heterozygosity, phased haplotypes extending to entire chromosome arms, retrotransposon insertions and structural variants (SVs) including complex and somatic genomic rearrangements. A large number of SVs were phased, sequence assembled and experimentally validated. We re-analyzed published HepG2 datasets for allele-specific expression and DNA methylation and assembled an allele-specific CRISPR/Cas9 targeting map. We demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework.

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  • HepG2 is characterized by pronounced aneuploidy and copy number variations, with a hyperdiploid mosaic genome and extensive regions of loss of heterozygosity on chromosomes 6, 11, 14, and 22.

    “HepG2 is characterized by pronounced aneuploidy and changes in the number of genome copies (copy number variations, CNVs). According to whole genome sequencing (WGS) data, the line is in a hyperdiploid state with a mosaic genome structure: about 74% of the genome has a baseline copy number (CN) of two, while significant proportions are accounted for by regions with CN = 3 (15.5%) and CN = 4 (2.7%)”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [81]

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Authors
Zhou, B., Ho, S. S., Greer, S. U., Spies, N., Bell, J. M., Zhang, X., Zhu, X., Arthur, J. G., Byeon, S., Pattni, R., Saha, I., Huang, Y., Song, G., Perrin, D., Wong, W. H., Ji, H. P., Abyzov, A., & Urban, A. E.
Affiliations
  • Stanford Medicine (US)
  • National Institute of Standards and Technology (US)
  • Stanford University (US)
  • Pusan National University (KR)
  • Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Queensland University of Technology (AU)
  • Mayo Clinic (US)
Corresponding author
  • Ho, Steve S
  • Spies, Noah
  • Arthur, Joseph G
  • Urban, Alexander E
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2019-03-13
Volume
47
Issue
8
Pages
3846-3861
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkz169
PMC
PMC6486628
OpenAlex
W2952980424
Cited by
72
References
5
Citations by year
2026: 9 · 2025: 11 · 2024: 11 · 2023: 4 · 2022: 13 · 2021: 7 · 2020: 11 · 2019: 5 · 2017: 1
FWCI
5.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, other-oa)
Funders
  • NIH
  • NHGRI (P50-HG007735, R01-HG007834, R01-HG006137, P01-HG00205)
  • NHLBI (T32-HL110952)
  • NSF (DGE-114747)
  • NIGMS (T32-GM096982)
  • NCI (U24CA220242)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
HepG2 cells, haplotype phasing, aneuploidy, copy number variation, structural variants, loss of heterozygosity, retrotransposon insertion, somatic rearrangements, allele-specific expression, DNA methylation, genome assembly, hepatocellular carcinoma
MeSH terms
Alleles, Aneuploidy, Chromosome Mapping, Haplotypes, Humans, Karyotyping, Genome, Human, Sequence Analysis, DNA, Retroelements, DNA Methylation, Loss of Heterozygosity, Polymorphism, Single Nucleotide, Genomics, INDEL Mutation, Genomic Structural Variation, Hep G2 Cells, High-Throughput Nucleotide Sequencing

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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