Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines
- Broad Institute of MIT and Harvard, United States
- Division of Hematology/Oncology, Department of Medicine; Bakar Computational Health Sciences Institute; Institute for Human Genetics; University of California, San Francisco, United States
- Helen Diller Family Comprehensive Cancer Center, United States
Figures
Figure 1 with 5 supplements
Telomere content and related genomic features across human cell lines.
Cell lines were grouped by cancer type and ordered by telomere content within each type, and are displayed such that each column represents a cell line. Telomere content measurements reflect …
Figure 1—figure supplement 1
Overlap between cell lines represented in annotations.
Heatmap of cell lines (columns) and annotations (rows). Colored cells indicate cell lines profiled for specific annotations, and gray cells indicate cell lines missing annotations.
Figure 1—figure supplement 2
Telomere content agreement between sequencing sets.
(a) Pairwise correlations between cell lines in overlaps of the indicated sequencing sets. Telomere content estimates are displayed as z-scored values of log2-transformed raw content estimates. p …
Figure 1—figure supplement 3
Telomere content, age, and tissue subtype.
(a) Correlation between donor age and z-scored and log2 transformed telomere content estimates from CCLE WGS (left) and GDSC WES (right) telomere content estimates as labeled. (b) Correlation …
Figure 1—figure supplement 4
Transcriptomic associations between TERT, TERC, and telomere content.
(a and b) Pearson correlations between log2(TPM + 1) levels of TERT mRNA and telomere content within tissue subtypes in the CCLE WGS and GDSC WES datasets, respectively. CNS, central nervous system; …
Figure 1—figure supplement 5
Associations between telomere content and cell line characteristics.
(a) Distributions of z-scored log2-transformed telomere content estimates from merged CCLE WGS and GDSC WES estimates, stratified by mutations in TP53, ATRX, DAXX, IDH1, and VHL. Boxes, …
Figure 2 with 2 supplements
Telomere-binding protein dependencies are associated with telomere content and TP53 mutation status.
(a) Pairwise plot of Pearson correlations between dependencies of all genes in the Avana dataset and CCLE WGS telomere content (x-axis, n = 210–211 cell lines) and GDSC WES telomere content (y-axis, …
Figure 2—figure supplement 1
Telomere content and telomere protein dependencies.
(a) Scatterplots of z-scored log2-transformed telomere content estimates from the CCLE WGS (left) and GDSC WES (center) datasets against sensitivity to members of the CST complex measured in the …
Figure 2—figure supplement 2
TP53 mutation status and shelterin member dependencies.
(a) Codependencies of CST and shelterin complex members in the Avana CRISPR-Cas9 dataset as measured by Pearson correlation and the associated two-sided P value (n = 793–808 cell lines). q-values …
Figure 3 with 2 supplements
Allele-specific methylation of the TERT locus is indicative of both promoter mutation status and allele-specific expression.
(a) Heatmap of CpG methylation levels along the TERT locus, sorted in order of mean methylation levels along the upstream 5 kb region within TERTp-mutants and -wildtypes. TERT gene expression levels …
Figure 3—figure supplement 1
TERT promoter mutations, gene expression, and ASE.
(a) Frequencies of TERT promoter mutations across different tissue subtypes. (b) Distributions across different promoter mutation types of mRNA expression as measured in log2(TPM + 1) from RNAseq. …
Figure 3—figure supplement 2
Interactions bewteen TERT ASE, promoter mutations, and methylation.
(a) Contingency table of TERT allele-specific expression and TERT promoter mutation status. p Value determined by Fisher’s exact test. (b) Distribution of TERT allele-specific expression and …
Figure 4 with 1 supplement
TERT promoter mutations associate with genome-wide decreased methylation of PRC2-repressed regions.
(a) Pairwise plot of median CGI methylation levels in TERTpmut cell lines (n = 21–83; Supplementary file 6) versus TERTpWT cell lines (n = 95–410, Supplementary file 6). Each dot represents a CGI. (b…
Figure 4—figure supplement 1
Global methylation changes associated with TERT promoter mutations.
(a) Genomic distribution of CGIs hypomethylated in TERTpmut CCLE cell lines. Shaded regions denote 10 Mb chromosome ends. (b) Methylation at the cg11625005 CpG probe and TERT mRNA expression across …
Additional files
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Supplementary file 1
Telomere content estimates and sample information.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp1-v2.xlsx
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Supplementary file 2
Telomere content and transcriptomic associations.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp2-v2.xlsx
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Supplementary file 3
Unsupervised dependency associations.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp3-v2.xlsx
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Supplementary file 4
Allele-specific expression calls.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp4-v2.xlsx
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Supplementary file 5
TERT locus methylation.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp5-v2.xlsx
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Supplementary file 6
Genome-wide methylation analysis in the CCLE.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp6-v2.xlsx
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Supplementary file 7
Genome-wide methylation analysis in TCGA.
- https://cdn.elifesciences.org/articles/66198/elife-66198-supp7-v2.xlsx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/66198/elife-66198-transrepform-v2.pdf
