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

                                                                                                                           Last updated June 15, 2016

Molecular studies of human carcinomas and sarcomas.

 


In our laboratory we study human tumors with the ultimate goal of developing new diagnostic markers, new biomarkers for prognosis and response to treatment and to develop novel therapeutic targets.  Within our group Rob West focuses on breast carcinoma, prostate carcinoma and head & neck tumors while Matt van de Rijn 's main interest is in sarcomas.  We use and develop a range of techniques that focus on extracting genomic and proteomic data from patient derived archival material (formalin-fixed paraffin-embedded (FFPE)).. 

Genomic analyses include RNAseq, exome seq and 3SEQ for gene expression profiling and mutation calling.  3SEQ(3’-end sequencing for expression quantification) is a novel procedure that we developed  for gene expression profiling from FFPE tissue using next-generation sequencing.  Tissue microarrays generated with FFPE material from thousands of tumor samples are analyzed with immunohistochemistry and in situ hybridization techniques to validate findings from the molecular studies. We now have over 500,000 digital images from these TMA’s stored in our image database, TMAD

 

Some examples of ongoing studies in the lab are:

-) Ductal carcinoma in situ progression in breast cancer (Dr.West)


With the advent of screening mammography, there has been a remarkable rise in the diagnosis of DCIS among asymptomatic women without the expected reduction in breast cancer mortality, leading to concerns about both over-diagnosis and over-treatment.  We use whole exome sequencing, whole genome sequencing and RNA sequencing to identify genomic and phenotypic changes in DCIS that develop IBC (high risk) versus cases of DCIS that do not develop IBC.  We are studying patient cohorts, including cohorts from the Nurses’ Health Study (NHS). We are also developing new technologies to allow us to perform gene expression profiling on specimens for which no frozen tissue is available. For example we are combing FFPE-based NGS with laser capture microdissection to capture localized microscopic entities such as in situ carcinoma and precursors thereof. This work is supported by funding from the NIH.

 

-) Prostate cancer (Dr.West)

Recent suggests that in the U.S. prostate cancer is over-detected and over-treated resulting in significant morbidity and financial costs. While many prostate cancers should be managed with active surveillance, uncertainties surrounding available clinical tools of aggressiveness (such as PSA, Gleason score and clinical stage) will often drive patients and physicians to treatment. We hypothesize that early prostate cancer arises from definable molecular alterations in precursor lesions and progresses as a result of acquired lesions that confer aggressive features in a subpopulation of cells in precursor lesions and/or early tumors. We are defining the earliest genomic events on the pathway to invasive carcinoma to examine the key genomic features distinguishing good and bad outcome prostate cancer. We are using technologies we have developed to analyze small samples in both fixed and frozen tissue to provide a complete picture of the early events in prostate carcinogenesis. This work is supported by funding from the NIH.

 

-) Head & Neck cancer  (Dr.West)

Our focus in head and neck cancers is current on nasopharyngeal carcinoma (NPC) and ameloblastoma. 

NPC is a malignant neoplasm of the nasopharynx with a high incidence in Southern Asia and in other endemic areas.  Though it is exquisitely sensitive to radiation (XRT), NPC remains clinically challenging due to distant metastases.  There is an urgent need to understand which patients are at risk for distant metastases and to tailor therapy for these patients.  Biomarkers for NPC outcome are limited.  We hypothesize that NPCs differ in the type and accumulation of genomic alterations and that measuring these will help us identify cases that have a high likelihood of progressing to distant metastases and poor outcomes. We are generating a clinical classifier of risk by combining the most informative features from these genomic analyses. Our goal is to provide more relevant and predictive clinical results to patients at the time of diagnosis that will more appropriately guide immediate therapy with the ultimate goal of reducing incidence of and mortality from NPC, while at the same time avoiding unnecessary interventions.

Ameloblastoma is a rare but aggressive tumor of the jaws.  We have recently identified driver mutations in both mandibular and maxillary ameloblastomas which has lead to a clinical trial at Stanford.  We are currently pursuing genomic studies to identify additional biomarkers that would predict response and aid in diagnosis.

This work is supported by funding from the Stanford Cancer Center.

 

-) Leiomyosarcoma (Dr. van de Rijn)

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. In our most recent work we confirmed the existence of molecular subtypes in LMS. Future studies will investigate the clinical relevance of these findings, specifically the sensitivity of each subtype to current clinical treatment modalities and therapies that are under development, such as the CD47-based approach. In collaboration with the laboratories of Drs. Ash Alizadeh and Max Diehn at Stanford, we are studying circulating tumor DNA in LMS patients. The goal is to use the levels of circulating LMS DNA as a measurement for tumor in the patient and to evaluate the response to therapy. Our work on LMS work is supported by donations from Leiomyosarcoma Direct Research, the National Leiomyosarcoma Foundation and the Liddy Shriver Initiative.

 

-) Gastrointestinal stromal tumor (Dr. van de Rijn)


While clinically relevant GIST is extremely rare, small (< 1cm) GIST are quite common.  We are performing a study that tries to identify the molecular changes in “mini-GISTs” to clinically significant tumors. This work is supported in part by funding from Life Raft Group.

 

-) Desmoid type fibromatosis (Dr. van de Rijn)


We are studying desmoid type fibromatosis, using gene expression profiling and tissue microarray analysis with the intent of identifying diagnostic markers for this tumor and to finding novel targets for therapy.   This work is supported by the Desmoid Tumor Research Foundation.

 

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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