Project description:Purpose 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 in tumour samples compared to normal samples. This study aimed to identify whether DNA methylation contributed to these gene expression changes in the same breast cancer cohort. Additionally, we aimed to identify a whole genome methylation profile that contributes to the progression from primary breast tumour to lymph node metastasis. Methods We used the DNA of 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues to perform 450K Illumina methylation arrays. The results were validated in an independent cohort of 70 primary TNBC samples. Results The gene expression of 16/38 TNBC-specific genes was associated with significantly altered methylation. Furthermore, altered methylation of 18 genes associated with lymph node metastasis was identified and validated in an independent cohort. Additionally, novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Conclusion This study has shown that DNA methylation plays an important role in altered gene expression patterns of TNBC-specific genes and is the first study to perform whole genome DNA methylation analysis that includes matched lymph node metastases in this breast cancer subtype. This novel insight into the progression of TNBC to secondary cancers may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. study cohort
Project description:Purpose 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 in tumour samples compared to normal samples. This study aimed to identify whether DNA methylation contributed to these gene expression changes in the same breast cancer cohort. Additionally, we aimed to identify a whole genome methylation profile that contributes to the progression from primary breast tumour to lymph node metastasis. Methods We used the DNA of 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues to perform 450K Illumina methylation arrays. The results were validated in an independent cohort of 70 primary TNBC samples. Results The gene expression of 16/38 TNBC-specific genes was associated with significantly altered methylation. Furthermore, altered methylation of 18 genes associated with lymph node metastasis was identified and validated in an independent cohort. Additionally, novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Conclusion This study has shown that DNA methylation plays an important role in altered gene expression patterns of TNBC-specific genes and is the first study to perform whole genome DNA methylation analysis that includes matched lymph node metastases in this breast cancer subtype. This novel insight into the progression of TNBC to secondary cancers may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. Validation cohort (70 IDC TNBC samples)
Project description:Genome-wide DNA methylation profiling of of 44 matched primary breast tumors and metastases. We sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome (n=44) and transcriptome (n=36) of matched primary breast tumors and regional metastases.
Project description:DNA methylation was generated from 11 pairs of matched primary-metastases medulloblastoma samples using the Illumina Infinium HumanMethylation450 BeadChip array
Project description:DNA methylation was generated from 11 pairs of matched primary-metastases medulloblastoma samples using the Illumina Infinium HumanMethylation450 BeadChip array Total DNA was extracted from primary and metastases medulloblastoma samples, bisulfite converted and hybridized to Illumina Infinium HumanMethylation450 BeadChip according to the manufacturer's instructions.
Project description:Exome and whole genome sequencing of matched primary tumor and lung metastases was used to identify metastasis-specific genomic events that drive metastasis.