Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

Breast Cancer Research

C Marcelo Aldaz¹  Keith Baggerly³  Aysegul Sahin²  Sally Gaddis¹  Cintia Notcovich¹  Hongxia Sun¹  Yuhui Hu¹  Kathleen A Hawkins¹  Jeffrey A Drake¹  Martin C Abba¹ 

[1] Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park – Research Division, Smithville, Texas, USA;Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

关键词: serial analysis of gene expression;    gene expression profiling;    breast cancer;   

Others  :  1118730
DOI  :  10.1186/bcr899

 received in 2004-03-02, accepted in 2004-05-25,  发布年份 2004

【 摘 要 】

Introduction

Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution.

Methods

In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed.

Results

We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01).

Conclusion

A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions with fully invasive lesions, a much more heterogeneous group, clearly identified as the most importantly deregulated group of transcripts those encoding for various families of proteins in charge of extracellular matrix remodeling, invasion and cell motility functions.

【 授权许可】

   
2004 Abba et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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