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Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma.

Dong H, Qian Z, Zhang L, Chen Y, Ren Z, Ji Q - Genom Data (2015)

Bottom Line: Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015) (GEO#: GSE65486).In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions.We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations) in this cohort of the patients.

View Article: PubMed Central - PubMed

Affiliation: AstraZeneca Asian and Emerging Market iMed, Zhangjiang Hi-Tech Park, Shanghai, PR China.

ABSTRACT
Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC) development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015) (GEO#: GSE65486). In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations) in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration.

No MeSH data available.


Related in: MedlinePlus

(a).Overlapping view of interactions between HCC genetics lesions and HBV variants. MLL4 fusion (blue fill), gene mutations (red fill), and MET amplification (orange fill) were aligned to HBV genotypes and DR1 mutants (blank: wild type, red: mutant, gray, no reads covered). (b) Linkage disequilibrium analyses of all HBV mutations detected in current study revealed DR1 region is functional important for HCC.
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f0005: (a).Overlapping view of interactions between HCC genetics lesions and HBV variants. MLL4 fusion (blue fill), gene mutations (red fill), and MET amplification (orange fill) were aligned to HBV genotypes and DR1 mutants (blank: wild type, red: mutant, gray, no reads covered). (b) Linkage disequilibrium analyses of all HBV mutations detected in current study revealed DR1 region is functional important for HCC.

Mentions: In a previous paper, we reported that HBV transcripts were detected in 88% (44/50) of the HCC samples, of which 77% (34/44) exhibited HBV genotype C, and 23% (10/44) were HBV genotype B. Expression of HBV transcription showed a segmented pattern with four peaks identified in the HBx-pre core region, prior to HBx, pre-S2, and S regions. In those HBV expressed regions, we further identified HBV mutations which occurred frequently in the 33 HBV genotype C positive patients. Moreover, high frequency of mutations identified at the important HBV regulatory regions of core promoter (nucleotides 1751–1769), DR1 (nucleotides 1824–1835), epsilon (nucleotides 1847–1907) and poly A signal (nucleotides 1916–1921). They included 14.8% T1753C, 54.2% A1762T, 33.3% G1764A, 52.2% C1827A, 42.9% A1846C/T, 21.3% G1896A, 21.4% C1913A and 21.4% G1915C. Among those HBV mutations, A1753, A1762 and G1764 are located within HBV ORF X. The others, A1846, G1896, C1913 and G1915 are located within pre-core/core ORF, which all were relevant to HCC carcinogenesis [5]. We categorized HBV variations and high frequent mutant human genes in Fig. 1a.


Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma.

Dong H, Qian Z, Zhang L, Chen Y, Ren Z, Ji Q - Genom Data (2015)

(a).Overlapping view of interactions between HCC genetics lesions and HBV variants. MLL4 fusion (blue fill), gene mutations (red fill), and MET amplification (orange fill) were aligned to HBV genotypes and DR1 mutants (blank: wild type, red: mutant, gray, no reads covered). (b) Linkage disequilibrium analyses of all HBV mutations detected in current study revealed DR1 region is functional important for HCC.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664659&req=5

f0005: (a).Overlapping view of interactions between HCC genetics lesions and HBV variants. MLL4 fusion (blue fill), gene mutations (red fill), and MET amplification (orange fill) were aligned to HBV genotypes and DR1 mutants (blank: wild type, red: mutant, gray, no reads covered). (b) Linkage disequilibrium analyses of all HBV mutations detected in current study revealed DR1 region is functional important for HCC.
Mentions: In a previous paper, we reported that HBV transcripts were detected in 88% (44/50) of the HCC samples, of which 77% (34/44) exhibited HBV genotype C, and 23% (10/44) were HBV genotype B. Expression of HBV transcription showed a segmented pattern with four peaks identified in the HBx-pre core region, prior to HBx, pre-S2, and S regions. In those HBV expressed regions, we further identified HBV mutations which occurred frequently in the 33 HBV genotype C positive patients. Moreover, high frequency of mutations identified at the important HBV regulatory regions of core promoter (nucleotides 1751–1769), DR1 (nucleotides 1824–1835), epsilon (nucleotides 1847–1907) and poly A signal (nucleotides 1916–1921). They included 14.8% T1753C, 54.2% A1762T, 33.3% G1764A, 52.2% C1827A, 42.9% A1846C/T, 21.3% G1896A, 21.4% C1913A and 21.4% G1915C. Among those HBV mutations, A1753, A1762 and G1764 are located within HBV ORF X. The others, A1846, G1896, C1913 and G1915 are located within pre-core/core ORF, which all were relevant to HCC carcinogenesis [5]. We categorized HBV variations and high frequent mutant human genes in Fig. 1a.

Bottom Line: Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015) (GEO#: GSE65486).In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions.We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations) in this cohort of the patients.

View Article: PubMed Central - PubMed

Affiliation: AstraZeneca Asian and Emerging Market iMed, Zhangjiang Hi-Tech Park, Shanghai, PR China.

ABSTRACT
Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC) development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015) (GEO#: GSE65486). In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations) in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration.

No MeSH data available.


Related in: MedlinePlus