Gene Expression Signatures of High Risk MGUS to Multiple Myeloma transitions and Uses Thereof (17 GENE PROFILE)

Application: Prognostic Test / Diagnostic Screening Multiple Myeloma and other cancers

The condition of monoclonal gammopathy of undetermined significance (MGUS) is a buildup of monoclonal antibodies produced by abnormal but non-cancerous plasma cells. People with a monoclonal gammopathy of undetermined significance often remain stable for years and do not require treatment. However, for unknown reasons, in about one quarter of people with these disorders, there is a progression to a cancerous disorder, such as multiple myeloma, or other disorders often after many years. This progression cannot be prevented, but if detected early, symptoms and complications of the cancerous disorder may be prevented or treated sooner.

The diagnostic to detect the transition of MGUS to multiple myeloma at an early stage has been developed through the identification and development of a gene array profile which is highly predictive of the disease progression. Starting with microarray analysis on the tumor cells from 532 newly diagnosed multiple myeloma patients, a signature gene profile has been developed with provides an indication of whether a benign condition of monoclonal gammopathy of undetermined significance (MGUS) will progress to multiple myeloma or remain stable.

Through a multivariate discriminate analysis a minimal gene set of 17 genes has been demonstrated to predict outcomes as well as a gene set containing many more genes. These data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression and that expression profiling can be used to identify this high-risk disease and guide therapeutic intervention.

Earlier Related Patent Applications:

“TP53 Gene Expression Prognostic Factor in Multiple Myeloma” I07-06

“Gene Expression Profiling Multiple Myeloma and Uses Thereof” I07-01

“Gene Expression Profiling to Predict Survival in Cancer Patients" I04-12-1 (I05-05); I04-12CIP

“Diagnosis and Prognosis of Multiple Myeloma Based on Gene Expression Profiling" I02-08-1 (I05-06); I02-08-1CIP; CIP2; 1CIP3 {05-06}; CIP4 {05-21}

No known limitations at this time

File Number: 07-24 

Web site: http://www.uams.edu/bioventures/

Disease: Cancer

Other Information:

US-2008-0274911-A1 published 11/6/08

US-2008-0187930-A1 published 8/7/08

WO2008/057545 republished 12/24/08

Current and Future Development Focus
The 17 gene profile microarray has been verified in Stage I testing using a data set of 532 patients. In addition, verification of the model has been shown through independent trials and data sets, including at the Mayo Clinic. The research team is currently considering redeveloping this array using the RT-PCR approach, as microarrays have not yet been approved by the FDA for use on patients. However, the FDA is currently using this model to assist in determining whether or not to allow microarrays for use in patient diagnostics.