Somatic mutation and clonal evolution normal breast tissue WGS
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ABSTRACT:
PROVIDER: EGAS00001002857 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (<20 to >70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development.
| EGAS00001002858 | EGA
Project description:Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (<20 to >70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development. .
This dataset contains all the data available for this study on 2023-03-09.
| EGAD00001010123 | EGA
Project description:Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (<20 to >70 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumour development. .
This dataset contains all the data available for this study on 2020-01-15.
| EGAD00001005787 | EGA
Project description:Gene expression in histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients share a similar profile Introduction: We hypothesized that gene expression in histologically normal epithelium (NlEpi) would differ in breast cancer patients (HN) compared to usual-risk controls undergoing reduction mammoplasty (RM), and that gene expression in NlEpi from cancer-free prophylactic mastectomies from high-risk women (PM), would resemble HN gene expression. Methods: We analyzed gene expression in 73 NlEpi samples microdissected from frozen tissue. In 42 cases, we used Affymetrix HU133A microarrays to compare gene expression in 18 RM vs 18 age-matched HN (9 ER+, 9 ER-) and 6 PM. Data were validated with qPCR in 31 independent NlEpi samples (8 RM, 17 HN, 6 PM). Results: 98 probesets (86 genes) were differentially expressed between RM and HN samples. Perfoming supervised hierarchical analysis with these 98 probesets, PM and HN samples clustered together, away from RM samples. qPCR validation of independent samples was high (84%) and uniform in RM vs HN, and lower (58%), but more heterogeneous, in RM vs PM. The 86 genes were implicated in many processes including transcription and the MAPK pathway. Conclusion: Gene expression differs between NlEpi of cancer cases and controls. The cancer cases' profile can be discerned in high-risk NlEpi. This suggests that the profile is not an effect of the tumor, but may mark increased risk and reveal breast cancer's earliest genomic changes. We determined that 98 probesets significantly differed between reduction mammoplasty and histologically normal epithelium from breast cancer patients. We also found that the histologically normal epithelium from prophylactic mastectomy patients' gene expression was more similar to histologically normal epithelium from breast cancer patients' than to reduction mammoplasty patients' gene expression. These results demonstrate that gene expression differs between NlEpi of cancer cases and controls. The cancer casesâ?? profile can be discerned in high-risk NlEpi. This suggests that the profile is not an effect of the tumor, but may mark increased risk and reveal breast cancer's earliest genomic changes. 42 total laser capture microdissected histologically normal breast tissue samples were analyzed with Affymetrix HU133A microarrays. 36 samples were age-matched between reduction mammoplasty (n=18) and histologically normal epithelial samples from breast cancer patients (n=18; 9ER+, 9ER-). 6 histologically normal epithelial samples from prophylactic mastectomy patients were then compared to data generated from the original 36 sample comparison. Sample numbers correspond to individual patient samples.
2010-06-08 | E-GEOD-20437 | biostudies-arrayexpress
Project description:Gene expression profiling of normal tissues after curative radiotherapy was carried out to investigate the pathogenesis of late radiation injury in humans. Irradiated and control normal breast tissue was collected from patients undergoing bilateral mastectomy for ipsilateral tumour relapse or prophylaxis following radiotherapy for breast cancer. Using P.A.L.M. laser capture microdissection (LCM) of frozen sections, breast tissue was separated into an epithelial compartment (terminal duct lobular units and ducts) and a stromal compartment (remaining tissue). RNA was extracted, amplified and hybridised to a 20k cDNA array against a breast tissue reference RNA. Expression profiles of irradiated vs control breast were compared for each tissue compartment
2008-08-12 | E-TABM-419 | biostudies-arrayexpress
Project description:The purpose of this study was to understand the metabolomic changes in a breast tissue microenvironment at various stages of cancer development and progression (i.e. normal breast, DCIS, and invasive cancer). The goal of this metabolomics pilot and feasibility study was to apply a broad spectrum GC-MS metabolomics method to determine whether changes in normal tissue of women with cancer correlate with progression and or the subtype of the disease.
2014-04-30 | ST000054 | MetabolomicsWorkbench
Project description:The aim of our study is to examine the region of tissue surrounding or adjacent to breast tumor in order to detect pre-malignant histological and genetic changes that may be predictive of risk of breast cancer. In this study, histological and gene expression data of breast tissue were obtained from patients that underwent mastectomy at various stages of breast carcinoma. For each patient, samples were obtained from the tumor region and four surrounding zones (1cm, 2cm, 3 cm and 4 cm away from the grossly visible tumor boundary), where possible. We have also breast samples from healthy individuals undergoing breast reduction surgery (mammoplasty). Microarray gene expression profiles of tissue samples (tumor and surrounding tissue, and breast reduction mammoplasty) was performed. In addition pathologist reviewed all slides to provide a details histology of all samples (excluding breast mammoplasty)
2008-04-13 | E-TABM-276 | biostudies-arrayexpress
Project description:Gene expression in histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients share a similar profile Introduction: We hypothesized that gene expression in histologically normal epithelium (NlEpi) would differ in breast cancer patients (HN) compared to usual-risk controls undergoing reduction mammoplasty (RM), and that gene expression in NlEpi from cancer-free prophylactic mastectomies from high-risk women (PM), would resemble HN gene expression. Methods: We analyzed gene expression in 73 NlEpi samples microdissected from frozen tissue. In 42 cases, we used Affymetrix HU133A microarrays to compare gene expression in 18 RM vs 18 age-matched HN (9 ER+, 9 ER-) and 6 PM. Data were validated with qPCR in 31 independent NlEpi samples (8 RM, 17 HN, 6 PM). Results: 98 probesets (86 genes) were differentially expressed between RM and HN samples. Perfoming supervised hierarchical analysis with these 98 probesets, PM and HN samples clustered together, away from RM samples. qPCR validation of independent samples was high (84%) and uniform in RM vs HN, and lower (58%), but more heterogeneous, in RM vs PM. The 86 genes were implicated in many processes including transcription and the MAPK pathway. Conclusion: Gene expression differs between NlEpi of cancer cases and controls. The cancer cases' profile can be discerned in high-risk NlEpi. This suggests that the profile is not an effect of the tumor, but may mark increased risk and reveal breast cancer's earliest genomic changes. We determined that 98 probesets significantly differed between reduction mammoplasty and histologically normal epithelium from breast cancer patients. We also found that the histologically normal epithelium from prophylactic mastectomy patients' gene expression was more similar to histologically normal epithelium from breast cancer patients' than to reduction mammoplasty patients' gene expression. These results demonstrate that gene expression differs between NlEpi of cancer cases and controls. The cancer cases’ profile can be discerned in high-risk NlEpi. This suggests that the profile is not an effect of the tumor, but may mark increased risk and reveal breast cancer's earliest genomic changes.
2010-06-01 | GSE20437 | GEO
Project description:Emerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumor. Matched tumor, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select breast epithelial cells from normal tissues, and neoplastic cells from tumor specimens for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal breast and tumor tissue (63,271 CpG loci q < 0.01), than between ipsilateral-normal tissue and tumor (38,346 CpG loci q < 0.01). In addition, we identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p < 0.01). Hypomethylated loci in ipsilateral normal relative to contralateral were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3. Hypermethylated loci in ipsilateral-normal relative to contralateral-normal tissue were significantly enriched for CpG island shore regions.
2020-07-10 | GSE133985 | GEO
Project description:Histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients
| PRJNA125611 | ENA