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Connective Tissue Oncology Society

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2002 CTOS Annual Meeting Posters — Biology

IDENTIFICATION OF A SINGLE NUCLEOTIDE POLYMORPHISM IN THE MMP-1 PROMOTER IN CHONDROSARCOMA
[Abstract ID: 8]

Category: Biology

Authors: Ian Douglas Dickey1, Sean Patrick Scully1

Author Institutions: 1Mayo Clinic, Minnesota, United States

Presenter: Ian Douglas Dickey
dickey.ian@mayo.edu

Correspondent: Ian Douglas Dickey
dickey.ian@mayo.edu
Rochester Minnesota United States 55905
Ph: 507-538-2424
Fax: 507-284-5075


Objectives:  Matrix Metalloproteinases (MMPs) are a group of enzymes that facilitate cellular invasion via the degradation of the extracellular matrix. Specifically their ability to degrade collagen types III and I is important in tumor invasion and metastasis. Over expression of the MMP-1 gene has been shown to correlate with poorer outcome. The level of expression of this gene is significantly increased by the presence of a single nucleotide polymorphism in the MMP-1 promoter sequence as a result of the creation of an Ets binding site. This SNP results from the addition of a single guanine base at –1607bp.

Methods:  Looking at both a chondrosarcoma cell line and a series of 10 clinical samples, after D.N.A. extraction, purification, polymerase chain reaction and sequencing, we identified the presence of the single nucleotide polymorphism at –1607bp within the promoter for MMP-1.

Results:  A complete set of genotypes was found suggesting that possibly the clinical behavior of some tumors could be influenced by the genotype resulting in a mechanism for more aggressive biologic behavior locally and distantly. This was correlated with the clinical outcome of the patient with respect to local disease status and suggested that patients with the S.N.P. were at greater risk of developing local recurrence despite wide surgical margins.

Conclusions:  This discovery of this S.N.P. in Chondrosarcoma and its possible correlation to local recurrence and ultimately long term survival may provide a very useful tool in predicting patient outcome. Studies of a larger numbers are required to further elucidate this possible relationship.


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