Myriad Genetics, Inc.

Other

University of Utah Research Foundation

University of Texas System

University of Pennsylvania

Endorecherche, Inc.

The United States of America As Represented by the Department of Health

The United States of America As Represented by the Secretary of Health

Myraid Genetics, Inc.

The Hospital for Sick Children

Hsc Research and Development Limited Partnership

Hsc Reseach & Development Limited Partnership

Myriad Genectics, Inc.

Hsc Research & Development Limited Parntership

Sean V Tavtigian

Alexander Kamb

Johanna Rommens

Jacques Simard

Peter A Steck

Mark A Pershouse

Samar A Jasser

Mark H Skolnick

Alfred W K Yung

Donna M Shattuck-Eidens

Paul L Bartel

P Andrew Futreal

Keith D Harshman

Jeff Swenson

David E Goldgar

Yoshio Miki

Roger W Wiseman

Alexander K C Wong

David H Teng

David H F Teng

Fergus Couch

Barbara L Weber

David H-f Teng

Alexander K Wong

Steven Stone

W K Alfred Yung

Ping Jiang

Lisa A Cannon Albright

Susan L Neuhausen

Brad Swedlund

David H -f Teng

William L Perry, Iii

Johanna M Rommens

A specific region of chromosome 10 (10q23.3) has been implicated by series of studies to contain a tumor suppressor gene involved in gliomas, as well as a number of other human cancers. One gene within this region was identified, and the corresponding coding region of the gene represents a novel 47 kD protein. A domain of this product has an exact match to the conserved catalytic domain of protein tyrosine phosphatases, indicating a possible functional role in phosphorylation events. Sequence analyses demonstrated the a number of exons of the gene were deleted in tumor cell lines used to define the 10q23.3 region, leading to the classification of this gene as a tumor suppressor. Further analyses have demonstrated the presence of a number of mutations in the gene in both glioma and prostate carcinoma cells. Methods for diagnosing and treating cancers related to this tumor suppressor, designated as TS10q23.3, also are disclosed.

Tumor suppressor designated TS10Q23.3

Tumor suppressor designated TS10q23.3

The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human prostate cancer predisposing gene (HPC2), some alleles of which cause susceptibility to cancer, in particular prostate cancer. More specifically, the present invention relates to germline mutations in the HPC2 gene and their use in the diagnosis of predisposition to prostate cancer. The invention also relates to presymptomatic therapy of individuals who carry deleterious alleles of the HPC2 gene. The invention further relates to somatic mutations in the HPC2 gene in human prostate cancer and their use in the diagnosis and prognosis of human prostate cancer. Additionally, the invention relates to somatic mutations in the HPC2 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the HPC2 gene, (including gene therapy, protein replacement therapy, protein mimetics, and inhibitors). The invention further relates to the screening of drugs for cancer therapy. Finally, the invention relates to the screening of the HPC2 gene for mutations, which are useful for diagnosing the predisposition to prostate cancer.

Chromosome 17P-linked prostate cancer susceptibility gene

The present invention relates to the relation of the BRG1 gene (also called SNF2&agr;) to human cancers and its use in the diagnosis and prognosis of human cancer. The invention also relates to the therapy of human cancers which have a mutation in the BRG1 gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

BRG1 is a tumor suppressor that is mutated in prostate and other cancer types

The present invention relates to the relation of the TMPRSS2 gene to human cancers and its use in the diagnosis and prognosis of human cancer. The invention also relates to the therapy of human cancers which have a mutation in the TMPRSS2 gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

TMPRSS2 is a tumor suppressor

A human gene which is here named CA7 CG04 has been identified in which mutations have been found which have been correlated with prostate cancer.

Prostate cancer susceptible CA7 CG04 gene

The present invention is directed to the MMSC1 gene, its protein product and the use of the protein to (i) detect mutant MMAC1 proteins, (ii) screen for drugs which can be used for suppressing tumor growth and (iii) identify proteins which interact with the MMAC1 gene or are involved in the tumor suppression pathway of the MMAC1 gene.

MMSC1-an MMAC1 interacting protein

The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human prostate cancer predisposing gene (HPC2), some alleles of which cause susceptibility to cancer, in particular prostate cancer. More specifically, the present invention relates to germline mutations in the HPC2 gene and their use in the diagnosis of predisposition to prostate cancer. The invention also relates to presymptomatic therapy of individuals who carry deleterious alleles of the HPC2 gene. The invention further relates to somatic mutations in the HPC2 gene in human prostate cancer and their use in the diagnosis and prognosis of human prostate cancer. Additionally, the invention relates to somatic mutations in the HPC2 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the HPC2 gene, (including gene therapy, protein replacement therapy, protein mimetics, and inhibitors). The invention further relates to the screening of drugs for cancer therapy. The invention also relates to the screening of the HPC2 gene for mutations, which are useful for diagnosing the predisposition to prostate cancer. In addition, the invention relates to a paralog of human HPC2, the paralog being named ELAC1, and to orthologs of human HPC2, these being mouse Elac2, chimpanzee Elac2 and gorilla Elac2.

Chromosome 17p-linked prostate cancer susceptibility gene and a paralog and orthologous genes

The present invention relates generally to the field of human genetics. Specifically, the present invention relates to human CDC14A gene which has been found to be mutated in certain tumor cell lines. More specifically, the invention relates to a novel sequence for the human CDC14A gene. The present invention further relates to somatic mutations in the CDC14A gene in human cancer and their use in the diagnosis and prognosis of human cancer. The invention also relates to the therapy of human cancers which have a mutation in the CDC14A gene, including gene therapy, protein replacement therapy and protein mimetics. The invention further relates to the screening of drugs for cancer therapy. Finally, the invention relates to the screening of the CDC14A gene for mutations, which are useful for diagnosing the predisposition to cancer.

Human CDC14A gene

The present invention is directed to the MMSC2 gene, its protein product and the use of the protein to (i) detect mutant MMAC1 proteins, (ii) screen for drugs which can be used for suppressing tumor growth and (iii) identify proteins which interact with the MMAC1 gene or are involved in the tumor suppression pathway of the MMAC1 gene.

MMSC2&mdash;an MMAC1 interacting protein

Recent evidence indicates that the carboxy-terminal region of the tumor suppressor protein BRCA1 is a functionally significant domain. Using the yeast two-hybrid assay and an in vitro biochemical assay, it is here shown that a protein, B112, interacts specifically with the carboxy-terminal segment of human BRCA1 from residue 1602 to 1863. A germ line truncation mutation, 1853ter, that removes the last 11 amino acids from the carboxy-terminus of BRCA1 abolishes not only the transcription activation function, but also binding to B112. The B112 protein is apparently the same as an uncharacterized protein known as CtIP, the sequence of which was previously deposited in GenBank. Screenings of a panel of 92 tumor cell lines for mutations in the B112/CtIP sequence have identified a number of missense variants, including a non-conserved lysine to glutamic acid change at codon 337 in the pancreatic cancer line, BxPC3. Taken together, these results indicate that B112/CtIP participates in a common biochemical pathway as BRCA1 and that the interaction of these two proteins may be required for the tumor suppressor function of BRCA1.

Carboxy-terminal BRCA1 interacting protein

Growing community of inventors

Salt Lake City, UT, United States of America

Sean V Tavtigian