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:This microarray dataset contains 51 triple-negative breast cancers with clinical and recurrence information for at least 3 years of follow-up and 106 luminal breast cancers (reanalyzed data from Series GSE24124, GSE9309, and GSE17040). A novel set of 45-gene signature that was statistically predictive of distant metastasis recurrence for triple-negative breast cancer was identified in this study.
Project description:Discrepancies in the prognosis of triple negative breast cancer exist between Caucasian and Asian populations. Yet, the gene signature of triple negative breast cancer specifically for Asians has not become available. Therefore, the purpose of this study is to construct a prediction model for recurrence of triple negative breast cancer in Taiwanese patients.
Project description:Discrepancies in the prognosis of triple negative breast cancer exist between Caucasian and Asian populations. Yet, the gene signature of triple negative breast cancer specifically for Asians has not become available. Therefore, the purpose of this study is to construct a prediction model for recurrence of triple negative breast cancer in Taiwanese patients. Whole genome expression profiling of breast cancers from 185 patients in Taiwan from 1995 to 2008 was performed, and the results were compared to the previously published literature to detect differences between Asian and Western patients. Pathway analysis and Cox proportional hazard models were applied to construct a prediction model for the recurrence of triple negative breast cancer. Most expression data of samples (181/185) were reanalyzed from previous studies already uploaded to GEO (see "reanalysis of" links below). Four additional gene expression profiling data of triple negative breast cancer sample were added to this study.
Project description:The aim of this study was evaluate the transcriptome changes in the comparison between triple negative tumors with increased SPARC expression and triple negative tumors with decreased SPARC expression according to Nagai et al., 2011 (Breast Cancer Res Treat (2011) 126:1–14) The results generated could be of particular interest to better define the prognostic impact of SPARC expression in triple negative breast tumors
Project description:This phase I trial is studying the side effects and best dose of giving 7-hydroxystaurosporine together with irinotecan hydrochloride in treating patients with metastatic or unresectable solid tumors, including triple-negative breast cancer (currently enrolling only patients with triple-negative breast cancer since 6/8/2007). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving 7-hydroxystaurosporine together with irinotecan hydrochloride may help kill more cancer cells by making tumor cells more sensitive to the drug.