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DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients

View Article: PubMed Central - PubMed

ABSTRACT

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC-specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype.

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Related in: MedlinePlus

Unsupervised Hierarchical clustering of the DNA methylation of the significant 16/38 TNBC specific genes.Primary tumour TNBC (IDC) samples are shown in red and matched normal adjacent tissue (NAT) samples are shown in blue in the sample tree on the left (y-axis). Genes are clustered along the x-axis. Hypomethylation is shown in blue, hypermethylation is shown in red and equivocal methylation is shown in grey.
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f3: Unsupervised Hierarchical clustering of the DNA methylation of the significant 16/38 TNBC specific genes.Primary tumour TNBC (IDC) samples are shown in red and matched normal adjacent tissue (NAT) samples are shown in blue in the sample tree on the left (y-axis). Genes are clustered along the x-axis. Hypomethylation is shown in blue, hypermethylation is shown in red and equivocal methylation is shown in grey.

Mentions: We found that 16 of the 38 TNBC-specific genes were associated with differentially methylated probes in the study and validation cohorts (41 probes) (Table 2 and Fig. 3). A set of five genes (ANKRD30B, COL14A1, IGF1, IL6ST, MEG3) exhibited regional methylation differences (28 probes) in both cohorts. Three of which showed very strong methylation changes in both cohorts (>20% methylation change), these were ANKRD30B (7 hyper-methylated probes), COL14A1 (6 hyper-methylated probes), and MEG3 (8 hyper-methylated probes). Of the four TNBC-specific genes that were common in both analyses in our previous study, there was one (IL6ST) that showed significantly altered methylation in 3 probes in both cohorts (Table 2). The methylation change for IL6ST can be classed as a DMR. However, no probes within these regions were significantly associated with survival (data not shown).


DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients
Unsupervised Hierarchical clustering of the DNA methylation of the significant 16/38 TNBC specific genes.Primary tumour TNBC (IDC) samples are shown in red and matched normal adjacent tissue (NAT) samples are shown in blue in the sample tree on the left (y-axis). Genes are clustered along the x-axis. Hypomethylation is shown in blue, hypermethylation is shown in red and equivocal methylation is shown in grey.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037364&req=5

f3: Unsupervised Hierarchical clustering of the DNA methylation of the significant 16/38 TNBC specific genes.Primary tumour TNBC (IDC) samples are shown in red and matched normal adjacent tissue (NAT) samples are shown in blue in the sample tree on the left (y-axis). Genes are clustered along the x-axis. Hypomethylation is shown in blue, hypermethylation is shown in red and equivocal methylation is shown in grey.
Mentions: We found that 16 of the 38 TNBC-specific genes were associated with differentially methylated probes in the study and validation cohorts (41 probes) (Table 2 and Fig. 3). A set of five genes (ANKRD30B, COL14A1, IGF1, IL6ST, MEG3) exhibited regional methylation differences (28 probes) in both cohorts. Three of which showed very strong methylation changes in both cohorts (>20% methylation change), these were ANKRD30B (7 hyper-methylated probes), COL14A1 (6 hyper-methylated probes), and MEG3 (8 hyper-methylated probes). Of the four TNBC-specific genes that were common in both analyses in our previous study, there was one (IL6ST) that showed significantly altered methylation in 3 probes in both cohorts (Table 2). The methylation change for IL6ST can be classed as a DMR. However, no probes within these regions were significantly associated with survival (data not shown).

View Article: PubMed Central - PubMed

ABSTRACT

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC-specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype.

No MeSH data available.


Related in: MedlinePlus