Clinical implications of chromatin accessibility in human cancers

Volume 11, Issue 18 of @Oncotarget Clinical implications of chromatin accessibility assessed by ATAC-seq profiling in human cancers especially in a large patient cohort is largely unknown.

In this study, the authors analyzed ATAC-seq data in 404 cancer patients from the Cancer Genome Atlas, representing the largest cancer patient cohort with ATAC-seq data, and correlated chromatin accessibility with patient demographics, tumor histology, molecular subtypes, and survival.

Chromatin accessibility, especially on the X chromosome, is strongly dependent on patient sex, but not much on patient age or tumor stage.

Dr. Yuexin Liu from The Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA said, "Cancer is a heterogeneous disease with a diversity of cell types which thus play a deterministic role on patient outcome or therapeutic responses."

"Cancer is a heterogeneous disease with a diversity of cell types which thus play a deterministic role on patient outcome or therapeutic responses."

- Dr. Yuexin Liu, The Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center

The assay for transposase-accessible chromatin using sequencing employs hyperactive Tn5 transposase for highly efficient cutting of exposed DNA and simultaneous ligation of adapters which are then subject to next-generation sequencing.

Therefore, ATAC-seq has enabled the genome-wide profiling of chromatin accessibility in primary human cancers.

Unexpectedly, there is little research on cancer study by using the ATAC-seq technique with a limited number of cancer types such as prostate cancer, pancreatic cancer, and hematological malignancy.

Figure 1: Chromosomal landscape of chromatic accessibility in human cancers. (A) Distribution of all the regulatory elements such as promoter, enhancer, intron, and other elements across chromosomes. Here the other elements denote elements located at the exonic region, or 3′ UTR, or 5′ UTR. Color indicates the type of genomic region overlapped by the peak. UTR, untranslated region. (B) Genome landscapes of chromatin accessibility. The chromatin accessibility scores indicate the likelihood of chromatin openness and are plotted in two-dimensional space representing chromosomal positions of human genome assembly (GRCh38). One dimension consists of the 23 chromosomes from Chr1 to ChrX and the other dimension indicates the genomic coordinates on a chromosome from p arm to q arm. Correlation of the colors and accessibility scores is indicated by the accompanied colorbar.

Recently, the Cancer Genome Atlas performed ATAC-seq on 410 tumor samples derived from 404 unique donors and generated a catalog of chromatin accessibility in human cancers.

We will further integrate ATAC-seq data along with the patient clinical annotations or molecular characteristics to determine the association between chromatin accessibility in the promoter regions and patient demographics such as sex, age, tumor stage and histology, molecular subtype, and patient survival.

The Liu Research Team concluded in their Oncotarget Research Article, "chromatin accessibility has important clinical implications in human cancers and our results provide an additional perspective in tumor initiation and progression."

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DOI - https://doi.org/10.18632/oncotarget.27584

Full text - https://www.oncotarget.com/article/27584/text/

Correspondence to - Yuexin Liu - yliu8@mdanderson.org

Keywords - ATAC-seq, chromatin accessibility, TCGA, promoter, survival

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