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Assessment of tumor heterogeneity, as evidenced by gene expression profiles, pathway activation, and gene copy number, in patients with multifocal invasive lobular breast tumors

ABSTRACT: Assessment of tumor heterogeneity, as evidenced by gene expression profiles, pathway activation, and gene copy number, in patients with multifocal invasive lobular breast tumors

PROVIDER: PRJNA315100 | ENA |

REPOSITORIES: ENA

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Assessment of tumor heterogeneity, as evidenced by gene expression profiles, pathway activation, and gene copy number, in patients with multifocal invasive lobular breast tumors [gene copy number]

2016-04-30 | GSE79170 | GEO

Assessment of tumor heterogeneity, as evidenced by gene expression profiles, pathway activation, and gene copy number, in patients with multifocal invasive lobular breast tumors [gene expression]

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Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors.

Project description:Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC.We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5 mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual.35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT.There was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed.

| S-EPMC4831790 | biostudies-literature

Assessment of tumor heterogeneity, as evidenced by gene expression profiles, pathway activation, and gene copy number, in patients with multifocal invasive lobular breast tumors

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-04-30 | GSE79171 | GEO

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Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines

2016-01-05 | E-GEOD-68057 | biostudies-arrayexpress

Transcription profiling of human lobular and ductal invasive carcinomas vs normal breast tissue from the same patient to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells

Project description:The aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition, TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas. Ten surgical specimens obtained by mastectomy from postmenopausal patients with invasive ductal (IDC) and lobular breast (ILC) carcinomas were investigated. Of these, 5 were IDCs and 5 were ILCs. Tumor and normal tissues from the same mammary gland were identified by an experienced pathologist, snap-frozen in liquid nitrogen and stored at -80ÂºC for further analysis. Microdissection, RNA isolation, amplification, labeling and microarray analysis are described in sample definitions. Samples from particular cell types (normal ductal, normal lobular, tumor ductal, tumor lobular - 10, 10, 5, 5 samples, respectively) were considered as biological replicates and were compared in between.

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