Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Breast Cancer RNA-seq

ABSTRACT: RNA-seq was performed on breast cancer cell lines and primary tumors RNA-seq was performed on 28 breast cancer cell lines, 42 Triple Negative Breast Cancer (TNBC) primary tumors, and 42 Estrogen Receptor Positive (ER+) and HER2 Negative Breast Cancer primary tumors, 30 uninovlved breast tissue samples that were adjacent to ER+ primary tumors, 5 breast tissue samples from reduction mammoplasty procedures performed on patients with no known cancer, and 21 uninvolved breast tissue samples that were adjacent to TNBC primary tumors.

ORGANISM(S): Homo sapiens

SUBMITTER: Katherine Varley

PROVIDER: E-GEOD-58135 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Recurrent read-through fusion transcripts in breast cancer.

Varley Katherine E KE Gertz Jason J Roberts Brian S BS Davis Nicholas S NS Bowling Kevin M KM Kirby Marie K MK Nesmith Amy S AS Oliver Patsy G PG Grizzle William E WE Forero Andres A Buchsbaum Donald J DJ LoBuglio Albert F AF Myers Richard M RM

Breast cancer research and treatment 20140615 2

Read-through fusion transcripts that result from the splicing of two adjacent genes in the same coding orientation are a recently discovered type of chimeric RNA. We sought to determine if read-through fusion transcripts exist in breast cancer. We performed paired-end RNA-seq of 168 breast samples, including 28 breast cancer cell lines, 42 triple negative breast cancer primary tumors, 42 estrogen receptor positive (ER+) breast cancer primary tumors, and 56 non-malignant breast tissue samples. We ...[more]

PMID: 24929677

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Project description:Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. From the total of 4405 proteins identified (FDR<5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2) and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Upregulation of putative biomarkers in lymph node positive (vs. negative) luminal A tumors was validated by gene expression analysis of an independent published dataset (N=343) for CPB1 (p=0.00155), PDLIM2 (p=0.02027) and RELA (p=0.00015). Moreover, statistically significant connections with patient survival were identified in another public dataset (N=1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-κB pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor sub-population of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy.

Dataset Information

Breast Cancer RNA-seq

Publications

Recurrent read-through fusion transcripts in breast cancer.

Similar Datasets

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