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Series GSE100850 Query DataSets for GSE100850
Status Public on Oct 16, 2018
Title Epigenetic alterations detected in the genome of very young breast cancer patients: identification of new biomarkers
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Breast cancer in very young women (< 35 years BCVY) presents more aggressive and complex biological features than in their older counterparts. In this study we aimed to identify the key pathways that may cause cancer in this younger age group. EPIC and 450k Illumina methylation arrays were used to identify differences in DNA methylation in 74 breast cancer tumours, including 37 from very young women. Additionally, we analysed copy number variation (CNV) and DNAm age using methylation intensities from Illumina Infinium MethylationEPIC BeadChip.
Although we are able to identify aberrant CNV patterns in breast cancer samples, they were not highly specific to BCVY. However, we identified 2 219 CpG sites that were differently methylated in BCVY vs. older women (false discovery rate < 0.05 beta-value difference ± 0.1), with the general hypomethylation profile affecting genes involved in neuronal-system pathways, cell communication, and extracellular matrix organisation, as confirmed by our experimental data. Additionally, a specific hypermethylation profile comprising 502 CpG sites located mainly in open-sea regions distinguished BCVY from older patients. Pathway enrichment analysis showed that regions implicated in the hypermethylation profile were involved in regulating genes related to Notch signalling pathways, the immune system, DNA repair, and vesicular trafficking. Moreover, BCVY presented age acceleration comparing with older women.
The expression of genes regulated by differentially-methylated CpG sites was validated using both Cancer Genome Atlas genomic data and by qRT-PCR, the latter in an independent sample (n = 40). This validation highlighted that 186 genes were consistently deregulated, including consistent hypomethylation and higher expression of HOXD9, PCDH10, and HDAC5 genes when considering BCVY vs. BC. Thus, we propose HDAC5 hypomethylation as a possible early detection biomarker in BCVY, and moreover, HDAC5 inhibitors, such as LMK-235, may be useful in treating breast cancer tumours in young women
 
Overall design We extracted DNA from 26 samples from BCVY (< 35 years) and 15 samples from older women with breast cancer (BCO) (> 45 years). Normal tissue samples from very young women (NVY) (n = 2) and older women (NO) (n = 3) were also included in the methylation study. All DNA samples were hybridized to the Illumina Infinium MethylationEPIC BeadChip.
This Series represents 21 samples from BCVY (< 35 years) and 13 samples from older women with breast cancer (BCO) (> 45 years). Normal tissue samples from very young women (NVY) (n = 2) and older women (NO) (n = 3) .
 
Contributor(s) Oltra SS, Ribas G
Citation(s) 30258192
Submission date Jul 06, 2017
Last update date Jul 25, 2021
Contact name Sara OLTRA SANCHIS
E-mail(s) saraoltra4@gmail.com
Phone 961973540
Organization name INCLIVA
Department Medical Oncology
Lab Cancer Functional Genomics
Street address Avda Menéndez Pelayo, 4 accesorio
City Valencia
State/province Valencia
ZIP/Postal code 46010
Country Spain
 
Platforms (1)
GPL21145 Infinium MethylationEPIC
Samples (39)
GSM2695082 Normal Breast tissue_Old (200526210010_R01C01)
GSM2695083 Breast Cancer_Old (200526210010_R02C01)
GSM2695084 Breast Cancer_Old (200526210010_R03C01)
Relations
BioProject PRJNA393265

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
GSE100850_RAW.tar 696.1 Mb (http)(custom) TAR (of IDAT)
Processed data included within Sample table
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