Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of breast tumors and surrounding tissue to detect pre-malignant histological and genetic changes

ABSTRACT: 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)

ORGANISM(S): Homo sapiens

DISEASE(S): Breast Carcinoma

SUBMITTER: Aedin Culhane

PROVIDER: E-TABM-276 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome.

Cheng Alfred S L AS Culhane Aedín C AC Chan Michael W Y MW Chan Michael W Y MW Venkataramu Chinnambally R CR Ehrich Mathias M Nasir Aejaz A Rodriguez Benjamin A T BA Liu Joseph J Yan Pearlly S PS Quackenbush John J Nephew Kenneth P KP Yeatman Timothy J TJ Huang Tim H-M TH

Cancer research 20080301 6

Estrogen imprinting is used to describe a phenomenon in which early developmental exposure to endocrine disruptors increases breast cancer risk later in adult life. We propose that long-lived, self-regenerating stem and progenitor cells are more susceptible to the exposure injury than terminally differentiated epithelial cells in the breast duct. Mammospheres, containing enriched breast progenitors, were used as an exposure system to simulate this imprinting phenomenon in vitro. Using MeDIP-chip ...[more]

PMID: 18339859

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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.

Dataset Information

Transcription profiling of breast tumors and surrounding tissue to detect pre-malignant histological and genetic changes

Publications

Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome.

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