Recurrent Gene Fusions In Prostate Cancer

A technology for prostate cancer and fusion, which is applied in the direction of drug combination, microbial determination/inspection, instrument, etc.

Inactive Publication Date: 2012-12-05
RGT UNIV OF MICHIGAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although hematological cancers are often characterized by balanced, disease-specific chromosomal rearrangements, most solid tumors have a plethora of nonspecific chromosomal aberrations

Method used

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  • Recurrent Gene Fusions In Prostate Cancer
  • Recurrent Gene Fusions In Prostate Cancer
  • Recurrent Gene Fusions In Prostate Cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0360] Embodiment 1: ERG and ETV1 gene fusion

[0361] A. Materials and methods

[0362] Cancer Outlier Profile Analysis (COPA)

[0363] COPA analysis was performed on 132 gene expression datasets containing 10,486 microarray experiments in Oncomine 3.0. In addition, data from 99 expanded laser capture microdissected prostate tissue samples were included in the COPA analysis. COPA works in three steps. First, the gene expression values ​​are centered around the median and the median expression value for each gene is set to zero. Second, the median absolute deviation (MAD) was calculated and scaled to 1 by dividing each gene expression value by its MAD. Transformations were performed using median and MAD rather than mean and standard deviation so that outlier expression values ​​did not unduly affect distribution estimates and thus were preserved after normalization. Third, for each gene transform 75 of the expression values th 、90 th and 95 th Percentile tabulation, fo...

Embodiment 2

[0418] Example 2: ETV4 Gene Fusion

[0419] A.Materials and methods

[0420] Expression of ETS families in profiling studies

[0421] To investigate the expression of ETS family members in prostate cancer, two prostate cancer profiling studies (Lapointe et al., Proc Natl Acad Sci USA 2004; 101:811-6 and Tomlins et al., Science 2005;310:644-8). Genes with ETS domains were identified by Interpro filter 'Ets' (Interpro ID: IPR000418). Heat map images were generated in Oncomine using the "median-center per gene" option, and the color contrast was set to highlight the differential expression of ERG and ETV1.

[0422] sample

[0423] Prostate cancer samples (PCA1-5) were obtained from the radical prostatectomy series at the University of Michigan as part of the Specialized Program of Research Excellence in Prostate Cancer (S.P.O.R.E.) organizational core at the University of Michigan. All samples were collected after obtaining patient informed consent and academic review boar...

Embodiment 3

[0439] Embodiment 3: the detection of gene fusion RNA

[0440] This example describes the target capture, amplification and qualitative detection of RNA containing the sequences of four gene fusions: TMPRSS2:ETV1a, TMPRSS2:ETV1b, TMPRSS2:ERGa and TMPRSS2:ERGb in four independent qualitative assays ( IVT) using APTIMA formulation reagents and HPA detection, each incorporating appropriate target-specific oligonucleotides, primers and probes. Table 5 shows the sequences of the oligonucleotides used in the assay.

[0441] table 5

[0442]

[0443] A. Materials and methods

[0444] RNA target capture

[0445] Lysis buffer contained 15 mM monobasic sodium phosphate monohydrate, 15 mM disodium hydrogen phosphate anhydrous, 1.0 mM EDTA disodium dihydrate, 1.0 mM EGTA free acid, and 110 mM lithium lauryl sulfate, pH 6.7. The target capture reagent contained 250 mM HEPES, 310 mM lithium hydroxide, 1.88 M lithium chloride, 100 mM EDTA free acid, pH 6.4, and 250 μg / ml of 1 micron m...

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Abstract

Recurrent gene fusions in prostate cancer of androgen regulated genes or housekeeping genes and ETS family member genes are described. Compositions and methods having utility in prostate cancer diagnosis, research, and therapy are also provided.

Description

[0001] Cross References to Related Applications [0002] This application is a continuation-in-part of application serial number 11 / 825,552, filed July 6, 2007, which is a continuation-in-part of application serial number 11 / 519,397, filed September 12, 2006, serial number 11 / 519,397 Application Claims Provisional Patent Application Serial Nos. 60 / 716,436 filed September 12, 2005, 60 / 779,041 filed March 3, 2006, 60 / 730,358 filed October 27, 2005, and April 28, 2006 60 / 795,590, each of which is hereby incorporated by reference in its entirety. [0003] Statement Regarding Federally Sponsored Research or Development [0004] This invention was made under government grants CA069568, CA102872, and CA111275 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0005] The present invention relates to compositions and methods for cancer diagnosis, research and treatment, including but not limited to cancer markers. In...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2600/178C12Q2600/156C12Q1/6886C12Q2600/118C12Q2600/136A61P13/08A61P35/00G01N33/57434
Inventor 阿鲁·M·辛莱岩韩博昌达·库马尔
Owner RGT UNIV OF MICHIGAN
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