Myriad Genetics, Inc.

University of Utah Research Foundation

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

Hsc Research and Development Limited Partnership

Arcaris, Inc.

Myraid Genetics, Inc.

Hsc Reseach & Development Limited Partnership

Myriad Genectics, Inc.

Hsc Research & Development Limited Parntership

Alexander Kamb

Sean V Tavtigian

Mark H Skolnick

Donna M Shattuck-Eidens

Yoshio Miki

Roger W Wiseman

P Andrew Futreal

David E Goldgar

Jeff Swenson

Keith D Harshman

Johanna Rommens

Steven Stone

Jacques Simard

Ping Jiang

Fergus Couch

Barbara L Weber

Lisa A Cannon-Albright

Michael John Feldhaus

Johanna M Rommens

The present invention relates to somatic mutations in the Multiple Tumor Suppressor (MTS) gene in human cancers and their use in the diagnosis and prognosis of human cancer. The invention further relates to germ line mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkins lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

MTS2 gene

The present invention relates to the Multiple Tumor Suppressor (MTS) genes in mice, their expression products, and their homology to the human MTS genes. The human MTS genes are involved in human cancers. The invention is further related to the use of the MTS genes in the therapy, diagnosis and prognosis of human cancer. The invention further relates to mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkin's lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

Mouse MTS2 gene

The present invention relates to somatic mutations in the Multiple Tumor Suppressor (MTS) gene in human cancers and their use in the diagnosis and prognosis of human cancer. The invention further relates to germ line mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkin's lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

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 breast and ovarian cancer predisposing gene (BRCA1), some mutant alleles of which cause susceptibility to cancer, in particular breast and ovarian cancer. More specifically, the invention relates to germline mutations in the BRCA1 gene and their use in the diagnosis of predisposition to breast and ovarian cancer. The present invention further relates to somatic mutations in the BRCA1 gene in human breast and ovarian cancer and their use in the diagnosis and prognosis of human breast and ovarian cancer. Additionally, the invention relates to somatic mutations in the BRCA1 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 BRCA1 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 BRCA1 gene for mutations, which are useful for diagnosing the predisposition to breast and ovarian cancer.

17q-linked breast and ovarian cancer susceptibility gene

Antibodies specific for MTS2 Polypeptide

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 breast cancer predisposing gene (BRCA2), some mutant alleles of which cause susceptibility to cancer, in particular breast cancer. More specifically, the invention relates to germline mutations in the BRCA2 gene and their use in the diagnosis of predisposition to breast cancer. The present invention further relates to somatic mutations in the BRCA2 gene in human breast cancer and their use in the diagnosis and prognosis of human breast cancer. Additionally, the invention relates to somatic mutations in the BRCA2 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 BRCA2 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 BRCA2 gene for mutations, which are useful for diagnosing the predisposition to breast cancer.

Chromosome 13-linked breast cancer susceptibility gene

MTS1 gene

The present invention relates to a method for the comparative assessment of the level of specific nucleic acid sequences in samples derived from different sources. More specifically, the invention relates to a method using oligonucleotides covalently linked to a solid support, such as beads, to isolate specific labeled nucleic acid sequences from complex mixtures. The methods disclosed allow quantitative comparisons of the amount of nucleic acid of defined sequence in a plurality of different samples of nucleic acid, e.g., from different cells or tissues or from genetic libraries. Nucleic acids from the samples are labeled in such a fashion that the signals can be distinguished and compared following hybridization to the oligonucleotides on the beads. According to the invention, the solid supports with the hybridized nucleic acid may be retrieved, and the target nucleic acid eluted and analyzed. Furthermore, the invention provides a method for tagging individual clones from a cDNA library such that they can be identified uniquely and retrieved by hybridization to specific beads.

Methods for measuring relative amounts of nucleic acids in a complex

Vector containing MTS1E1.beta. gene

MTS1 gene mutations

Methods for detecting predisposition to cancer at the MTS gene

A method for determining the presence of polymorphisms, including mutations, in nucleic acids by using mass spectrometry is presented. The method requires amplification of the nucleic acid region to be analyzed followed by analysis by mass spectrometry and comparison of the obtained spectrum with spectra obtained from wild-type sequences and/or sequences known to contain the polymorphism. Differences between the spectra, either the appearance or disappearance of one or more peaks indicating a change in mass or a change in the height of one or more peaks indicating a change in the amount of nucleic acid of a specific mass, indicate the presence of a polymorphism. Variations of the method involve digestion of the amplified nucleic acid, e.g., by using restriction enzymes, nucleases or chemical methods, prior to analysis by mass spectrometry. The method can be applied to any type of nucleic acid including genomic DNA, CDNA and RNA. The method is especially well suited for performing routine genetic screening on a large scale for mutations known to be associated with a disease. The method is also appropriate for determining the presence of polymorphisms for other purposes, e.g., for genotyping or screening for mutations in a positional cloning project. A preferred approach is to amplify then digest the nucleic acid and then to analyze it via matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) using a neodymium-garnet laser and a 3-hydroxypicolinic acid matrix.

Mass spectrometry to assess DNA sequence polymorphisms

Mouse MTSI gene

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Salt Lake City, UT, United States of America

Alexander Kamb