Linked breast and ovarian cancer susceptibility gene

• US 5,693,473 A
• Filed: 06/07/1995
• Issued: 12/02/1997
• Est. Priority Date: 08/12/1994
• Status: Expired due to Term

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: Cancer Institute, Centre de recherche du CHUL, Myriad Genetics, Inc.
• Inventors: Emi, Mitsuuru, Nakamura, Yusuke, Simard, Jacques, Shattuck-Eidens, Donna M., Durocher, Francine
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): REES, DIANE
• Application Number:
  US08/480,784
• Time in Patent Office: 909 Days
• Field of Search: 435/6, 435/91.2, 536/23.1, 536/24.3, 536/24.33
• US Class Current: 435/6.12
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

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.

Claims

1. An isolated DNA comprising an altered BRCA1 DNA having at least one of the alterations set forth in Tables 12A, 14, 18 or 19 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:

1.

2. An isolated DNA comprising an altered BRCA1 DNA having one of the alterations set forth in Tables 12A or 14 with the provision that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:

1.

11. The isolated DNA of claim 2 wherein said altered BRCA1 DNA has the alteration comprising a deletion of AG in codon 23.

12. The isolated DNA of claim 2 wherein said altered BRCA1 DNA has the alteration comprising an insertion of a nucleotide C corresponding to a base number 5382 in SEQ ID NO:

1.

13. The isolated DNA of claim 2 wherein said altered BRCA1 DNA has the alteration comprising a deletion of 40 nucleotides corresponding to base numbers 1294-1333 in SEQ ID NO:

1.

14. The isolated DNA of claim 2 wherein said altered BRCA1 DNA has the alteration comprising a substitution of a G for the T corresponding to a base number 391 in SEQ ID NO:

17.

3. An isolated DNA comprising an altered BRCA1 DNA having one of the alterations set forth in Tables 18 or 19.

4. A nucleic acid probe specifically hybridizable to a human altered BRCA1 DNA and not to wild-type BRCA1 DNA, said altered BRCA1 DNA having one of the alterations set forth in Tables, 12A, 14, 18 or 19.

5. A nucleic acid probe specifically hybridizable to human altered BRCA1 DNA and not to wild-type BRCA1 DNA, said altered BRCA1 DNA having one of the alterations set forth in Tables 12A or 14 with the proviso that the alteration is not a deletion of four nucleotides corresponding to base numbers 4184-4187 in SEQ. ID. NO:

1.

6. A nucleic acid probe specifically hybridizable to human altered BRCA1 DNA and not to wild-type BRCA1 DNA, said altered BRCA1 DNA having one of the alterations set forth in Tables 18 or 19.

7. The nucleic acid probe of claim 6 wherein said altered BRCA1 DNA has the alteration comprising a deletion of AG in codon 23.

8. The nucleic acid probe of claim 6 wherein said altered BRCA1 DNA has the alteration comprising an insertion of a nucleotide C corresponding to a base number 5382 in SEQ ID NO:

1.

9. The nucleic acid probe of claim 6 wherein said altered BRCA1 DNA has the alteration comprising a deletion of 40 nucleotides corresponding to base numbers 1294-1333 of SEQ ID NO:

1.

10. The nucleic acid probe of claim 6 wherein said altered BRCA1 DNA has the ablation comprising a substitution of a G for the T corresponding to a base number 391 in SEQ ID NO:

17.