TY - JOUR
T1 - Clinical implications of chromatin accessibility in human cancers
AU - Liu, Yuexin
N1 - Publisher Copyright:
Copyright: © Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Assay for transposase-accessible chromatin using sequencing (ATAC-seq) has not yet been widely used in cancer research. 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, we 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. Our results showed that chromatin accessibility varies from chromosome to chromosome, and is different in different genomic regions along the same chromosome. Chromatin accessibility especially on the X chromosome is strongly dependent on patient sex, but not much on patient age or tumor stage. Striking difference in chromatin accessibility is observed between lung adenocarcinoma and lung squamous cell carcinoma, the two most common histological subgroups in lung cancer. Furthermore, chromatin accessibility was different between basal and non-basal breast cancer. Finally, we identified prognostic peaks in the promoter regions that were significantly correlated with survival. In particular, we identified six peaks in the ESR1 gene promoter region in the ATAC-seq profiling and found that the peak about 247 bp away from the transcription start site was significantly associated with better survival. In conclusion, our study provides an alternative mechanism underlying tumor prognosis.
AB - Assay for transposase-accessible chromatin using sequencing (ATAC-seq) has not yet been widely used in cancer research. 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, we 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. Our results showed that chromatin accessibility varies from chromosome to chromosome, and is different in different genomic regions along the same chromosome. Chromatin accessibility especially on the X chromosome is strongly dependent on patient sex, but not much on patient age or tumor stage. Striking difference in chromatin accessibility is observed between lung adenocarcinoma and lung squamous cell carcinoma, the two most common histological subgroups in lung cancer. Furthermore, chromatin accessibility was different between basal and non-basal breast cancer. Finally, we identified prognostic peaks in the promoter regions that were significantly correlated with survival. In particular, we identified six peaks in the ESR1 gene promoter region in the ATAC-seq profiling and found that the peak about 247 bp away from the transcription start site was significantly associated with better survival. In conclusion, our study provides an alternative mechanism underlying tumor prognosis.
KW - ATAC-seq
KW - Chromatin accessibility
KW - Promoter
KW - Survival
KW - TCGA
UR - http://www.scopus.com/inward/record.url?scp=85086087989&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086087989&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.27584
DO - 10.18632/oncotarget.27584
M3 - Article
C2 - 32405341
AN - SCOPUS:85086087989
SN - 1949-2553
VL - 11
SP - 1666
EP - 1678
JO - Oncotarget
JF - Oncotarget
IS - 18
ER -