National Institutes of Health, Public Health Service, HHS.
The technology describes the discovery of a novel gene encoding the DNA-binding factor, “Brother of the Regulator of Imprinted Sites”, BORIS, related to the unique, evolutionarily conserved, CTCF factor involved in regulation of genomic imprinting and cancer. Furthermore, it describes several splice variants of BORIS that translate into different proteins and antibodies of BORIS that can be used for diagnosis and treatment of cancer.
A very recent finding is that protein CTCF (expressed in all somatic tissues) binds, in a methylation-dependent manner, to the imprinting control regions thus allowing somatic cells to distinguish functionally maternal from paternal alleles. The new factor, BORIS, shares with CTCF the same spectrum of DNA sequence specificity and it is normally expressed only in germ cells of human gonads (when patterns of gene imprinting are re-established), but not in CTCF-expressing somatic cells.
Additionally, since cell-growth controlling CTCF has properties of a tumor suppressor gene, abnormal activation of BORIS upon cancerous transformation of somatic cells results in competition with the normal function of CTCF, thereby promoting tumor growth. The inventors found that antibodies against BORIS are present and can be detected in human blood serum taken from patients with cancer but not from healthy donors. Additionally, 14 new alternative splice forms of the BORIS polypeptide have been identified which show specificity to specific cancers, suggesting that circulating antibodies for specific BORIS splice variants in cancer patients can be associated with specific types or stages of malignant tumors.
Therefore, BORIS can be used in both diagnostic and therapeutic arenas: First, mutations in BORIS genomic locus or detection of encoded by the BORIS locus mRNAs or polypeptides expressed in any tissue besides normal gonads may be indicative of a pre-cancerous or cancerous state thus serving a diagnostic and/or prognostic purpose; and, second, targeting of abnormally activated BORIS should serve as a novel therapeutic approach to treat cancer.
BORIS Technology Can Have Three Major Applications
1. BORIS can be used as a therapeutic target for anti-cancer treatments.
2. BORIS expression can serve as a diagnostic marker for specific cancers other than testis.
3. Detection of antibodies against BORIS in blood serum samples can also be used as an indicator of pre-cancerous or cancerous condition existing.
Competitive Advantage of Our Technology
Cancer/testis (CT) genes, predominantly expressed in the testis (germ cells) and generally not in other normal tissues, are aberrantly expressed in human cancers. This highly restricted expression provides a unique opportunity to use these CT genes for diagnostics, immunotherapeutic, or other targeted therapies. BORIS is a newly described CT gene shown to be expressed in several cancers including lung, brain, uterine and endometrial among others and thus can be used as a novel diagnostic and therapeutic target.
This technology consists of the following patents and patent applications:
1. U.S. Patent Application No. 10/505,377 filed October 20, 2004 and all foreign counterparts [E-227-2001/0-US-03];
2. U.S. Patent Application No. 11/575,732 filed March 21, 2007 and all foreign counterparts [E-241-2004/0-US-04]; and
3. PCT Application No. PCT/US2007/7728 filed August 30, 2007 [E-117-2006/0-PCT-02]
Next Step: Teleconference
There will be a teleconference where the principal investigator will explain this technology. Licensing and collaborative research opportunities will also be discussed. If you are interested in participating in this teleconference please call or e-mail Mojdeh Bahar; (301) 435-2950; firstname.lastname@example.org. OTT will then e-mail you the date, time and number for the teleconference.Start Signature
Dated: November 9, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. E7-22820 Filed 11-21-07; 8:45 am]
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