The van de Rijn & West Lab In The Department of Pathology

Study of human soft tissue tumors and carcinomas using 3SEQ (3'-End Sequencing for Expression Quantification), Human Exonic Evidence-based Oligonucleotide (HEEBO) and tissue microarrays

 

We study a wide variety of tumors using 3SEQ, gene microarray and tissue microarray analysis.  We designed a novel procedure (3’-end sequencing for expression quantification (3SEQ)) for gene expression profiling from FFPE (Formalin Fixed Paraffin Embedded tissue) using next-generation sequencing. 3SEQ technology can be effectively utilized to perform gene expression profiling on the vast majority of archival tumor samples. 3SEQ.  Tissue microarrays generated with paraffin-embedded material from tumor samples are analyzed with immunohistochemistry and in situ hybridization techniques to validate findings from the 3SEQ and gene array analyses.  The goal of these studies is to develop better diagnostic markers for the many different types of sarcomas and carcinomas and in addition to identify prognostic markers these tumors.  Last but not least we use these approaches to discover novel potential therapeutic targets for these diseases that are tested in animal models.  We have developed a comprehensive system for high throughput analysis and storage of tissue immunostaining microarray data using software applications developed in our laboratory.

1) Leiomyosarcoma

We are using gene expression profiling and comparative genomic hybridization to determine genes that are involved in the malignant transformation of smooth muscle cells in a wide variety of locations.  This work is supported by the NIH and donations from The National Leiomyosarcoma Foundation and Leiomyosarcoma Direct Research.

2) Gastrointestinal stromal tumor

We study GIST stromal tumors using similar techniques and are especially involved in the development of new markers for this disease and the expression profiling of wild type GIST and GIST that have become resistant to adjuvant therapy. This work is supported in part by grants from Life Raft Group.

3) Using sarcomas to study normal stroma and tumor stroma

We use soft tissue tumors derived from fibroblasts, myofibroblasts, endothelial cells and other stromal components to define novel markers that may be used to distinguish different types of spindle cells in normal and tumor stroma. We are especially focusing on the influence of different types of tumor stroma in breast, ovary and colon carcinoma.  This work is supported by the NIH.

4) Tumor progression in breast cancer

The 3SEQ technology allows us to perform gene expression profiling on specimens for which no frozen tissue is available. For example precursors of invasive carcinoma of the breast routinely get entirely submitted for histologic examination in order to exclude the presence of invasive disease. 

5) Desmoid type fibromatosis

We are studying desmoid type fibromatosis, using gene expression profiling and tissue microarray analysis.   This work is supported by the Desmoid Tumor Research Foundation.

6) Non-coding RNA’s

Recently several new classes of RNA have been described.  One of these, lncRNA, can be detected through 3SEQ analysis and we are studying a wide range of human neoplasms to determine the differential expression of these molecules.

The studies mentioned above would be impossible to perform without the collaboration of a large number of colleagues at different institutions who not only supply us with material on tumors but also contribute their own technologies to these studies.  Our collaborators are listed on the “links”page.

 

 in situ hybridization

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