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Series GSE21994 Query DataSets for GSE21994
Status Public on May 29, 2010
Title Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities
Organism Mus musculus
Experiment type Expression profiling by array
Summary BACKGROUND: Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases.

METHODS AND FINDINGS: To identify alternative splicing events (ASEs) that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07) and highly metastatic (4T1) mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4%) exons and in 1725 out of 189,460 (1%) intronic regions, which affect 2623 out of 16,654 (16%) genes. These changes correspond to putative alternative isoforms-several of which are novel-that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1). These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers.

CONCLUSION: Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis-specific isoforms may contribute to the development of improved breast cancer stage identification and targeted therapies.
 
Overall design We used RNA tumor tissues derived from three murine mammary carcinoma cell lines (168FARN, 4T07 and 4T1); four biological replicates of 168FARN, four biological replicates of 4T07, and four biological replicates of 4T1 were hybridized independently at McGill university site.
 
Contributor(s) Bemmo A, Dias C, Rose AA, Russo C, Siegel P, Majewski J
Citation(s) 20700505
Submission date May 25, 2010
Last update date Mar 06, 2018
Contact name Amandine Bemmo
Organization name McGill University
Department Human Genetics
Lab McGill University and Genome Quebec Innovation Center
Street address 740, Dr Penfield Avenue
City Montréal
State/province Québec
ZIP/Postal code H3A 1A4
Country Canada
 
Platforms (2)
GPL6096 [MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version]
GPL6193 [MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [probe set (exon) version]
Samples (24)
GSM546937 168FARN biological replicate 1 (gene)
GSM546938 168FARN biological replicate 2 (gene)
GSM546939 168FARN biological replicate 3 (gene)
Relations
BioProject PRJNA127213

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21994_RAW.tar 937.1 Mb (http)(custom) TAR (of CEL)
GSE21994_probeset_dabg.txt.gz 183.2 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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