University of Arkansas

Bioventures, LLC

Other

Dana-farber-cancer Institute Inc.

John D Shaughnessy

Bart Barlogie

Fenghuang Zhan

Kenneth Carl Anderson

Ronald A DePinho

Lynda Chin

Ruben Carrasco

Giovanni Tonon

Cameron W Brennan

Ya-Wei Qiang

Uli Ruther

Jurgen Knobloch

Zhan Fenghuang

Gene expression profiling in multiple myeloma patients identifies genes that distinguish between patients with subsequent early death or long survival after treatment. Poor survival is linked to over-expression of genes such as ASPM, OPN3 and CKS1B which are located in chromosome 1q. Given the frequent amplification of 1q in many cancers, it is possible that these genes can be used as powerful prognostic markers and therapeutic targets for multiple myeloma and other cancer.

Use of gene expression profiling to predict survival in cancer patient

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifying genes directly involved in disease pathogensis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.

Diagnosis, prognosis and identification of potential therapeutic targets of multiple myeloma based on gene expression profiling

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifying genes directly involved in disease pathogensis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myeloma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.

The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.

Compositions, kits, and methods for identification, assessment, prevention, and therapy of cancer

The present invention is drawn to understanding lytic bone diseases. In this regard, the present invention discloses mechanism by which Wnt signaling antagonist inhibits bone differentiation. Also disclosed herein are methods to control bone loss, treat bone disease and prevent tumor growth in bones of individual.

Methods of increasing bone mass in a subject comprising inhibiting DKK1

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifying genes directly involved in disease pathogenesis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.

Methods of controlling bone loss by inhibiting DKK1

Provided herein is a method for gene expression profiling multiple myeloma patients into distinct subgroups via DNA hybridization and hierarchical clustering analysis of the hybridization data where the results may further be used to identify therapeutic gene targets. Also provided is a method for controlling bone loss in an individual via pharmacological inhibitors of DKK1 protein. In addition provided herein is a method for diagnosing multiple myeloma using a 15-gene model that classifies myeloma into groups 1-7.

Diagnosis, prognosis, identification, and classification of multiple myeloma based on gene expression profiling

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifing genes directly involved in disease pathogensis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.

Gene expression profiling based identification of CKS1B as a potential therapeutic target in multiple myeloma

Gene expression profiling between normal B cells/plasma cells and multiple myeloma cells revealed four distinct subgroups of multiple myeloma plasma cells that have significant correlation with clinical characteristics known to be associated with poor prognosis. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognostics for the four subgroups of multiple myeloma based on the expression of 24 genes were also established. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. The development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.

Diagnosis and classification of multiple myeloma

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of &#x2dc;12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with &#x2267;3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3/FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P&#x3c;0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to reduce tumor burden in multiple myeloma and to block bone disease.

Growing community of inventors

Little Rock, AR, United States of America

John D Shaughnessy