Next Generation Sequencing Approach to Desmoid Tumors

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Yan Guo Assistant Professor Department of Cancer Biology Vanderbilt University USA.

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Presentation transcript:

Next Generation Sequencing Approach to Desmoid Tumors Matt van de Rijn

Which questions do we hope to address? Can we distinguish aggressive desmoids from those that are indolent? Can we distinguish recurrent desmoid tumors from scars?

What do we need to know about biology? Each human cell contains a nucleus where the information for >20,000 genes resides Previously we could study genes one at a time Now can look at all of them simultaneously

Matt’s (simple) view of the cell: mRNA protein DNA RNA

Matt’s (simple) view of the cell: In each human cell: DNA: 3 billion basepairs mRNA: >20,000 genes

What is “next generation sequencing”? New technology in molecular biology that allows us to do work that used to take several years in one week First human genome took 10 years to sequence at a cost of >2 billion dollars Now can be done within a week at <$5,000

Dramatic shift in approach: Rather than sequencing long stretches of DNA (~700 bases) in relatively few experiments, we now sequence millions of very short fragments and let the computer figure out the overlap

3SEQ Uses Illumina Genome Analyzer for precise quantification of genome-wide mRNA expression levels on both frozen tissues and paraffin blocks PLoS One 2010, 5:e8768)

What’s a Paraffin Tissue Block?

Gene expression profiling by 3SEQ RNAseq DNAseq

Applications of paraffin block-based “3SEQ” Gene expression profiling -Characterization of fibroblastic lesions -Comparing desmoid tumors to scars Study of lncRNA expression as potential biomarker

collagenous fibroma (6) elastofibroma (4) Fibromatosis Elastofibroma Fibr Tendon Sheath Sol Fibrous tumor collagenous fibroma (6) elastofibroma (4) infantile digital fibromatosis (3) palmar fibromatosis (8) nasopharyngeal angiofibroma (6) fibroma of tendon sheath (4) nodular fasciitis (6) dermatofibrosarcoma protuberans (4) desmoid type fibromatosis (7) solitary fibrous tumor (5)

We no longer rely on rare frozen tissue specimens and can use readily available paraffin blocks Goal: To generate a clinically relevant predictor of desmoid behavior Plan: Compare desmoids with known aggressive behavior with those that never recurred and determine which markers can be used to distinguish them

Applications of paraffin block-based “3SEQ” Gene expression profiling -Characterization of fibroblastic lesions -Comparing desmoid tumors to scars Study of lncRNA expression as potential biomarker

Problem: When a desmoid comes back, it is difficult to tell recurring desmoid from the scar of the previous surgery Preliminary studies already identify possible markers Plan: Extend these studies and validate findings

Applications of paraffin block-based “3SEQ” Gene expression profiling -Characterization of fibroblastic lesions -Comparing desmoid tumors to scars Study of lncRNA expression as potential biomarker

Matt’s (simple) view of the cell: lncRNA mRNA protein DNA RNA

lncRNA’s detected by 3SEQ as specifically expressed in different malignancies Plan: Include desmoid tumors in this series to look for biologically relative lncRNAs

Thank you! Laboratory: Xiangqian Guo Sushama Varma Shirley Zhu Matt van de Rijn Rob West Santosh Gupta Trip Sweeney Erna Forgo Stanford Oncology: Kristen Ganjoo Stanford Surgery: Raffi Avedian DANA-Farber Oncology: Suzanne George Thank you!