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Expression data from tumor and normal epithelium derived from BRCA1-mutation carriers

ABSTRACT: Microarrays were used to determine relative global gene expression changes in WT and BRCA1-mutation carrier breast epithelium as well as tumors created from WT and BRCA1-mutation carrier breast epithelial cells. Total RNA was isolated from freshly dissociated mammary epithelilal cells obtained from disease-free prophylactic masectomy tissues of 4 different BRCA1-mutation carriers or 4 different reduction mammoplasty tissues from non-mutation carriers. Total RNA was also isolated from fresh tumor tissues derived from in vivo transformed human mammary epithelial cells created from cells obtained from WT or BRCA1-muation carrires. Dissociated mammary epithelial cells were transduced with lentiviruses encoding mutant p53, mutant ras, mutant PI3K and cyclin D1 and injected into in humanized glands. There were four tumor tissues isolated for each genetic background.

ORGANISM(S): Homo sapiens

SUBMITTER: Proia TA

PROVIDER: S-ECPF-GEOD-25835 | biostudies-other | 2011 Feb

REPOSITORIES: biostudies-other

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Expression data from tumor and normal epithelium derived from BRCA1-mutation carriers

2011-02-04 | GSE25835 | GEO

Expression data from tumor and normal epithelium derived from BRCA1-mutation carriers

Project description:Microarrays were used to determine relative global gene expression changes in WT and BRCA1-mutation carrier breast epithelium as well as tumors created from WT and BRCA1-mutation carrier breast epithelial cells. Total RNA was isolated from freshly dissociated mammary epithelilal cells obtained from disease-free prophylactic masectomy tissues of 4 different BRCA1-mutation carriers or 4 different reduction mammoplasty tissues from non-mutation carriers. Total RNA was also isolated from fresh tumor tissues derived from in vivo transformed human mammary epithelial cells created from cells obtained from WT or BRCA1-muation carrires. Dissociated mammary epithelial cells were transduced with lentiviruses encoding mutant p53, mutant ras, mutant PI3K and cyclin D1 and injected into in humanized glands. There were four tumor tissues isolated for each genetic background.

2011-02-04 | E-GEOD-25835 | biostudies-arrayexpress

Expression data from mammary epithelial cells from BRCA1 mutation carriers and non BRCA1 mutation carriers

Project description:Female BRCA1 mutation carriers have a nearly 80% probability of developing breast cancer during their life-time. We hypothesized that the breast epithelium at risk in BRCA1 mutation carriers harbors mammary epithelial cells (MECs) with altered proliferation and differentiation properties. Microarray studies revealed that PMEC colonies from BRCA1 mutation carriers anticipate expression profiles found in BRCA1-related tumors, and that the EGFR pathway is upregulated in BRCA1 mutation carriers compared ton non BRCA1 mutation carriers. Keywords: Class comparison and pathway analysis 10 colonies were collected and RNA was isolated using the Absolutely RNA Nanoprep kit, Stratagene. The arrays included duplicates from four normal controls and from two BRCA1 mutation carriers and single arrays from another two BRCA1 mutation carriers.

| S-ECPF-GEOD-13671 | biostudies-other

Normal human mammary tissues from BRCA1 mutation carriers, non-BRCA1/2 mutation carriers and normal women

Project description:Gene expression profiles of normal human mammary tissue from BRCA1 mutation carriers, non-BRCA1/2 mutation carriers and normal women. RNA was prepared from normal breast tissue (confirmed by pathology) from reduction mammoplasties (n=5) and prophylactic mastectomies of known BRCA1 (n=7) and non-BRCA1/2 mutation carriers (n=8). non-BRCA1/2 carriers were individuals with a strong family history of breast cancer (kConFab Category 1 (http://www.kconfab.org/Collection/Eligibility.shtml) where no mutation in BRCA1 or BRCA2 has been identified in the family by high sensitivity testing (http://www.kconfab.org/Progress/Sensitivity.shtml) of any individual affected by breast or ovarian cancer. Normal breast samples refer to reduction mammoplasty specimens, where family history is generally not known. Microarray expression profiles were obtained from whole pre-neoplastic breast tissue from three categories of patient, as described in the summary. Samples were checked for keratin gene expression levels as a marker for epithelium tissue, and a number of samples were removed because two or more keratin genes lacked detectable expression (BeadStudio detection p-value 0.01). One other sample was removed because its expression profile appeared abnormal. Out of 36 samples initially profiled, 20 passed the quality filters and were used for the final analysis.

| S-ECPF-GEOD-17072 | biostudies-other

Normal human mammary tissues from BRCA1 mutation carriers, non-BRCA1/2 mutation carriers and normal women

2009-08-01 | GSE17072 | GEO

Expression data from mammary epithelial cells from BRCA1 mutation carriers and non BRCA1 mutation carriers

2008-11-20 | GSE13671 | GEO

Normal human mammary tissues from BRCA1 mutation carriers, non-BRCA1/2 mutation carriers and normal women

2009-08-01 | E-GEOD-17072 | biostudies-arrayexpress

Expression data from mammary epithelial cells from BRCA1 mutation carriers and non BRCA1 mutation carriers

2008-11-19 | E-GEOD-13671 | biostudies-arrayexpress

Identification of a preneoplastic gene expression profile in tubal epithelium of BRCA1 mutation carriers.

Project description:Microinvasive carcinomas and high-grade intraepithelial neoplasms are commonly discovered within the fallopian tube of BRCA1 mutation carriers at the time of risk-reducing salpingo-oophorectomy, suggesting that many BRCA1-mutated ovarian carcinomas originate in tubal epithelium. We hypothesized that changes in gene expression profiles within the histologically normal fallopian tube epithelium of BRCA1 mutation carriers would overlap with the expression profiles in BRCA1-mutated ovarian carcinomas and represent a BRCA1 preneoplastic signature. Laser capture microdissection of frozen sections was used to isolate neoplastic cells or histologically normal fallopian tube epithelium, and expression profiles were generated on Affymetrix U133 Plus 2.0 gene expression arrays. Normal-risk controls were 11 women wild type for BRCA1 and BRCA2 (WT-FT). WT-FT were compared with histologically normal fallopian tube epithelium from seven women with deleterious BRCA1 mutations who had foci of at least intraepithelial neoplasm within their fallopian tube (B1-FTocc). WT-FT samples were also compared with 12 BRCA1 ovarian carcinomas (B1-CA). The comparison of WT-FT versus B1-FTocc resulted in 152 differentially expressed probe sets, and the comparison of WT-FT versus B1-CA resulted in 4079 differentially expressed probe sets. The BRCA1 preneoplastic signature was composed of the overlap between these two lists, which included 41 concordant probe sets. Genes in the BRCA1 preneoplastic signature included several known tumor suppressor genes such as CDKN1C and EFEMP1 and several thought to be important in invasion and metastasis such as E2F3. The expression of a subset of genes was validated with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.

| S-EPMC3003134 | biostudies-other

Immune cells are increased in normal breast tissues of BRCA1/2 mutation carriers.

Project description:PurposeBreast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities.MethodsWe assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests.ResultsNormal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors.ConclusionsThese preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.

| S-EPMC10168666 | biostudies-literature

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