Dataset Information

Individualized analysis reveals CpG sites with methylation aberrations in almost all lung adenocarcinoma tissues.

ABSTRACT:

Background

Due to the heterogeneity of cancer, identifying differentially methylated (DM) CpG sites between a set of cancer samples and a set of normal samples cannot tell us which patients have methylation aberrations in a particular DM CpG site.

Methods

We firstly showed that the relative methylation-level orderings (RMOs) of CpG sites within individual normal lung tissues are highly stable but widely disrupted in lung adenocarcinoma tissues. This finding provides the basis of using the RankComp algorithm, previously developed for differential gene expression analysis at the individual level, to identify DM CpG sites in each cancer tissue compared with its own normal state. Briefly, through comparing with the highly stable normal RMOs predetermined in a large collection of samples for normal lung tissues, the algorithm finds those CpG sites whose hyper- or hypo-methylations may lead to the disrupted RMOs of CpG site pairs within a disease sample based on Fisher's exact test.

Results

Evaluated in 59 lung adenocarcinoma tissues with paired adjacent normal tissues, RankComp reached an average precision of 94.26% for individual-level DM CpG sites. Then, after identifying DM CpG sites in each of the 539 lung adenocarcinoma samples from TCGA, we found five and 44 CpG sites hypermethylated and hypomethylated in above 90% of the disease samples, respectively. These findings were validated in 140 publicly available and eight additionally measured paired cancer-normal samples. Gene expression analysis revealed that four of the five genes, HOXA9, TAL1, ATP8A2, ENG and SPARCL1, each harboring one of the five frequently hypermethylated CpG sites within its promoters, were also frequently down-regulated in lung adenocarcinoma.

Conclusions

The common DNA methylation aberrations in lung adenocarcinoma tissues may be important for lung adenocarcinoma diagnosis and therapy.

SUBMITTER: Yan H

PROVIDER: S-EPMC5299650 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Individualized analysis reveals CpG sites with methylation aberrations in almost all lung adenocarcinoma tissues.

Yan Haidan H Guan Qingzhou Q He Jun J Lin Yunqing Y Zhang Juan J Li Hongdong H Liu Huaping H Gu Yunyan Y Guo Zheng Z He Fei F

Journal of translational medicine 20170208 1

<h4>Background</h4>Due to the heterogeneity of cancer, identifying differentially methylated (DM) CpG sites between a set of cancer samples and a set of normal samples cannot tell us which patients have methylation aberrations in a particular DM CpG site.<h4>Methods</h4>We firstly showed that the relative methylation-level orderings (RMOs) of CpG sites within individual normal lung tissues are highly stable but widely disrupted in lung adenocarcinoma tissues. This finding provides the basis of u ...[more]

PMID: 28178989

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Project description:BACKGROUND: The Human Papillomavirus (HPV) genome is divided into early and late coding sequences, including 8 open reading frames (ORFs) and a regulatory region (LCR). Viral gene expression may be regulated through epigenetic mechanisms, including cytosine methylation at CpG dinucleotides. We have analyzed the distribution of CpG sites and CpG islands/clusters (CGI) among 92 different HPV genomes grouped in function of their preferential tropism: cutaneous or mucosal. We calculated the proportion of CpG sites (PCS) for each ORF and calculated the expected CpG values for each viral type. RESULTS: CpGs are underrepresented in viral genomes. We found a positive correlation between CpG observed and expected values, with mucosal high-risk (HR) virus types showing the smallest O/E ratios. The ranges of the PCS were similar for most genomic regions except E4, where the majority of CpGs are found within islands/clusters. At least one CGI belongs to each E2/E4 region. We found positive correlations between PCS for each viral ORF when compared with the others, except for the LCR against four ORFs and E6 against three other ORFs. The distribution of CpG islands/clusters among HPV groups is heterogeneous and mucosal HR-HPV types exhibit both lower number and shorter island sizes compared to cutaneous and mucosal Low-risk (LR) HPVs (all of them significantly different). CONCLUSIONS: There is a difference between viral and cellular CpG underrepresentation. There are significant correlations between complete genome PCS and a lack of correlations between several genomic region pairs, especially those involving LCR and E6. L2 and L1 ORF behavior is opposite to that of oncogenes E6 and E7. The first pair possesses relatively low numbers of CpG sites clustered in CGIs while the oncogenes possess a relatively high number of CpG sites not associated to CGIs. In all HPVs, E2/E4 is the only region with at least one CGI and shows a higher content of CpG sites in every HPV type with an identified E4. The mucosal HR-HPVs show either the shortest CGI size, followed by the mucosal LR-HPVs and lastly by the cutaneous viral subgroup, and a trend to the lowest CGI number, followed by the cutaneous viral subgroup and lastly by the mucosal LR-HPVs.

Dataset Information

Individualized analysis reveals CpG sites with methylation aberrations in almost all lung adenocarcinoma tissues.

Background

Methods

Results

Conclusions

Publications

Individualized analysis reveals CpG sites with methylation aberrations in almost all lung adenocarcinoma tissues.

Similar Datasets

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