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Comparison between hereditary breast tumors and normal breast tissue samples

ABSTRACT: Tumor associated miRNAs in hereditary breast cancer. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling. Single color experiments in a pairwise comparison design.

ORGANISM(S): Homo sapiens

SUBMITTER: Martinez Beatriz

PROVIDER: S-ECPF-GEOD-32922 | biostudies-other |

REPOSITORIES: biostudies-other

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Comparison between hereditary breast tumors and normal breast tissue samples.

Project description:Tumor associated miRNAs in hereditary breast cancer. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling.

2013-12-01 | GSE32922 | GEO

Comparison between hereditary breast tumors and normal breast tissue samples.

2013-12-01 | E-GEOD-32922 | biostudies-arrayexpress

DNA Methylation in Ovarian Tumors-a Comparison Between Fresh Tissue and FFPE Samples.

Project description:Among women, ovarian cancer (OC) is one of the most severe forms of malignancy, accounting for a low 5-year survival rate, of approximately 52%. Early symptoms are unspecific and hence hard to detect. The origin of OC and its subtypes are still unclear, underlying the need for efficient diagnostic biomarkers. In that regard, epigenetics studies are emerging in cancer diagnostics, with encouraging outcomes. Among them, DNA methylation profiling has shown that the origins of the cancer epigenome are associated with molecular factors that are crucial to carcinogenesis, such as regulation of oncogenes and tumor suppressors. Furthermore, those events have been detected in abnormal cell morphology before neoplastic formation, indicating its potential crucial use in the OC diagnostics in the future. Nonetheless, studies are limited, and whether methylation analysis can be performed optimally in formalin-fixed paraffin-embedded (FFPE) preparations of OC cases is still elusive. In the present report, we investigated the performance of DNA methylation analysis in FFPE samples, compared to their matched fresh frozen tissue in a small cohort of OC samples. We found that the overall DNA methylation profile in FFPE tissue showed high concordance to that found in fresh frozen tissue, and accounting for the small cohort size, the differentially methylated sites found primarily in frozen tissue, compared to benign samples, were also reproducible in FFPE. Overall, by using samples from our current clinical setting of tissue preservation, these preliminary observations might provide insights into the clinical use of FFPE tissues in methylation studies without critically compromising the outcome.

| S-EPMC8526488 | biostudies-literature

Hereditary Breast Cancer Tumors

Project description:Genomic profile of 47 tumors from hereditary breast cancer cases by Array CGH, 7 of which were BRCA mutation carriers (4 in BRCA2 and 3 in BRCA1), previously analyzed for BRCA1 expression by immunohistochemistry. Our goal was to identify specific alterations for BRCA1 not expressing tumors

2015-07-07 | GSE70541 | GEO

Transcription profiling of human breast tissue tumors vs. normal tissue

Project description:bulk breast tumor RNA from patient; Abstract: Sporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors, most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic. total 62 sample incudes 43 tumor, 7 normal breast and 12 normal organelle Experiment Overall Design: compare expression of tumor to normal breast tissue

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Hereditary Breast Cancer Tumors

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Gene expression signatures of morphologically normal breast tissue identify basal-like tumors.

Project description:INTRODUCTION: The role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression in histologically normal tissue adjacent to breast tumor, if this is influenced by the tumor, and how this compares with non-tumor-bearing breast tissue. METHODS: To address this, we have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty (n = 44). RESULTS: Based on this data, we determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumor-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumor tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favorable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. CONCLUSION: Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression dataset for comparative studies of tumor expression profiles.

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Breast cancer and normal breast tissue samples to estimate the effect of contamination of breast cancer samples with normal breast tissue

Project description:PURPOSE: To estimate the effect of contamination with normal breast tissue for the development of gene signatures robust to pre-analytical conditions. METHODS: We evaluated the effect of contamination with normal breast tissue on gene signatures by comparing microarray profiles of breast cancer samples contaminated with increasing amounts of normal breast tissue.

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miRNA expression profiling in hereditary breast tumors

Project description:The objective of the study was to characterize hereditary breast tumors based on their miRNA expression profiles. To this end, we performed global miRNA expression analysis of more than 800 human miRNA genes in a large series of 80 FFPE breast tissue samples. The series included 66 hereditary breast primary tumors from 13 BRCA1 mutation carriers, 10 BRCA2 mutation carriers and 43 non-BRCA12 tumors denominated hereafter as BRCAX tumors. In addition we have analyzed 10 sporadic breast carcinomas and 4 normal breast tissues obtained after breast reduction surgery from healthy donors with no family history of breast cancer. To avoid contamination with normal breast tissue, tumoral area on FFPE blocks was marked by a pathologist and macrodissected for subsequent total RNA extraction. Microarray expression profiling was performed using miRCURY LNATM microRNA Array v.11 (Exiqon A/S, Denmark), in a single color experiments in a pairwise comparison experimantal design.

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Transcription profiling of surgical samples of primary brain tumors, normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors

Project description:Glioblastoma multiforme (GBM) is the most common form of malignant glioma and is characterized by marked genetic instability, extensive intra-tumoral histopathological variability, and unpredictable variation in its clinical behavior. We investigated global gene expression in surgical samples of primary brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix re-modeling. Significantly, we found that the global gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes that were more highly expressed in rapidly progressing tumors and which stratified GBMs into two groups that differed by more than four-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus provide a series of prognostic markers and suggest that their expression may enhance the invasive potential of tumor cells.

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