NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE213685 Query DataSets for GSE213685
Status Public on Apr 12, 2023
Title High-resolution Nanopore methylome-maps reveal random hyper-methylation at CpG-poor regions as driver of chemoresistance in leukemias. [methylation]
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Aberrant DNA-methylation at CpG dinucleotides is a hallmark of cancer and is associated with the emergence of resistance to anti-cancer treatment, though molecular mechanisms and biological signifi- cance remain elusive. Genome-scale methylation maps by currently used methods are based on chemical modification of DNA and are best suited for analyses of methylation at CpG-rich regions (CpG islands). We report the first high-coverage whole-genome map in cancer using the long-read nanopore technol- ogy, which allows simultaneous DNA-sequence and -methylation analyses on native DNA. We analyzed clonal epigenomic/genomic evolution in Acute Myeloid Leukemias (AMLs) at diagnosis and relapse, af- ter chemotherapy. Long-read sequencing coupled to a novel computational method allowed definition of differential methylation at unprecedented resolution (> 99% CpGs), extending analyses of CpG is- lands to sparse CpGs, which represent half of all differentially-methylated regions. We showed that the
 
Overall design relapse methylome is characterized by hypermethylation at both CpG islands and sparse CpGs. Hyper- methylated genes, however, only accounted for < 5% of all differentially-expressed genes (DEGs) in the relapsed AMLs and were not enriched for chemoresistance genes. A few under-expressed transcription- factors (1 to 6 in the different AMLs) hyper-methylated at sparse CpGs support ∼ 40% DEGs and are highly-enriched in chemoresistance genes. Hypermethylated regions at sparse CpGs were poorly con- served in the relapsed AMLs, under-represented at their genomic positions and showed high methylation- entropy, as compared to CpG islands. Relapsed AMLs carried a few patient-specific structural-variants and DNA-mutations, apparently not involved in drug-resistance. Thus, drug-resistance in AMLs is due to the selection of random epigenetic alterations at sparse CpGs of a few transcription factors, which then induce reprogramming of the relapsing phenotype, independently of clonal genomic-evolution.
 
Contributor(s) Magi A, Mattei G, Mingrino A, Caprioli C, Ronchini C, Frig`e G, Semeraro R, Bolognini D, Rambaldi A, Candoni A, Colombo E, Mazzarella L, Pelicci P
Citation(s) 37031307
BioProject PRJNA879930
Submission date Sep 19, 2022
Last update date Apr 13, 2023
Contact name Gianluca Mattei
E-mail(s) gianluca.mattei@unifi.it
Organization name Università degli Studi di Firenze
Street address Via di S. Marta, 3
City Firenze
State/province FI
ZIP/Postal code 50139
Country Italy
 
Platforms (1)
GPL28975 GridION (Homo sapiens)
Samples (6)
GSM6592040 AML patient (AML2), methylation table, relapse phase
GSM6592041 AML patient (AML2), methylation table, onset phase
GSM6592042 AML patient (UD5), methylation table, relapse phase
This SubSeries is part of SuperSeries:
GSE213686 High-resolution Nanopore methylome-maps reveal random hyper-methylation at CpG-poor regions as driver of chemoresistance in leukemias.

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE213685_RAW.tar 1019.8 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap