DAVID PAGE, MD
Medical Practice in Nashville, TN

6342483, Jan 29, 2002

Jan 15, 1998

09/007678

Jeffrey T. Holt - Brentwood TN
Roy A. Jensen - Franklin TN
David L. Page - Nashville TN
Patrice S. Obermiller - Nashville TN
Marilyn E. Thompson - Nashville TN

Vanderbilt University - Nashville TN

A61K 4800

514 44, 435455, 435456, 4353201, 435375

The present invention provides a method of detecting and diagnosing pre-invasive breast cancer by identifying differentially expressed genes in early, pre-invasive breast cancer tissue. Differentially expressed genes can be used as genetic markers to indicate the presence of pre-invasive cancerous tissues. Microscopically-directed tissue sampling techniques combined with differential display or differential screening of cDNA libraries are used to determine differential expression of genes in the early stages of breast cancer. Differential expression of genes in preinvasive breast cancer tissue is confirmed by RT-PCR, nuclease protection assays and in-situ hybridization of ductal carcinoma in situ tissue RNA and control tissue RNA. The present invention also provides a method of screening for compounds that induce expression of the BRCA1 gene, whose product negatively regulates cell growth in both normal and malignant mammary epithlial cells. The present invention also relates to gene therapy method using this gene.

5891857, Apr 6, 1999

Feb 20, 1996

8/603753

Jeffrey T. Holt - Brentwood TN
Roy A. Jensen - Franklin TN
Mary-Claire King - Seattle WA
David L. Page - Nashville TN
Csilla I. Szabo - Seattle WA
Thomas L. Jetton - Kingston Springs TN
Marilyn E. Thompson - Nashville TN

Vanderbilt University - Nashville TN
University of Washington - Seattle WA

A61K 4800

514 44

Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localizes to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroblasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described.

6149903, Nov 21, 2000

Jun 18, 1998

9/099753

Jeffrey T. Holt - Brentwood TN
Roy A. Jensen - Franklin TN
Mary-Claire King - Seattle WA
David L. Page - Nashville TN
Csilla I. Szabo - Seattle WA
Thomas L. Jetton - Kingston Springs TN
Marilyn E. Thompson - Nashville TN

Vanderbilt University - Nashville TN
University of Washington - Seattle WA

A61K 4800

424 932

Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localizes to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroblasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described.

5677125, Oct 14, 1997

Jan 14, 1994

8/182961

Jeffrey T. Holt - Franklin TN
Roy A. Jensen - Franklin TN
David L. Page - Nashville TN
Patrice S. Obermiller - Nashville TN

Vanderbilt University - Nashville TN

C12P 1934, C12Q 168

435 6

The present invention provides a method of detecting and diagnosing pre-invasive breast cancer by identifying differentially expressed genes in early, pre-invasive breast cancer tissue. Differentially expressed genes can be used as genetic markers to indicate the presence of pre-invasive cancerous tissues. Microscopically-directed tissue sampling techniques combined with differential display or differential screening of cDNA libraries are used to determine differential expression of genes in the early stages of breast cancer. Differential expression of genes in preinvasive breast cancer tissue is confirmed by RT-PCR, nuclease protection assays and in-situ hybridization of ductal carcinoma in situ tissue RNA and control tissue RNA.