Susceptibility mutation 6495delGC of BRCA2

• US 6,492,109 B1
• Filed: 09/21/1998
• Issued: 12/10/2002
• Est. Priority Date: 09/23/1997
• Status: Expired due to Term

• Current Assignee: Myriad Genetics, Inc.
• Original Assignee: Gene Logic, Inc. (Steel Partners Holdings LP)
• Inventors: Lescallet, Jennifer L., Thurber, Denise B.
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): WILDER, CYNTHIA B
• Application Number:
  US09/158,183
• Time in Patent Office: 1,541 Days
• Field of Search: 435/91.1, 435/320.1, 435/6, 435/69.1, 536/23.5, 536/24.31, 536/23.1, 536/24.3, 536/24.32, 536/24.33
• US Class Current: 435/6.14
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays

Abstract

A new mutation has been found in the BRCA2 gene. The mutation is a twobase pair deletion of nucleotide 6495 at nucleotides 6495 of the published cDNA sequence of BRCA2. A process for identifying a sequence variation in a BRCA2 polynucleotide sequence is disclosed. The identification process includes allele specific sequence-based techniques assays of known sequence variations. The methods can be used for efficient and accurate detection of a mutation in a test BRCA2 gene sample.

Claims

1. An isolated oligonucleotide that specifically hybridizes to a BRCA2 nucleotide sequence, wherein the BRCA2 nucleotide sequence comprises a two nucleotide deletion corresponding to positions 8 and 9 of SEQ ID NO:

3, relative to a BRCA2 nucleotide sequence that does not contain the deletion.

2. The isolated oligonucleotide of claim 1, wherein the BRCA2 nucleotide sequence encodes a protein of about 3418 amino acids.

3. The isolated oligonucleotide of claim 1, wherein the BRCA2 nucleotide sequence that encodes a BRCA2 protein is about 10,248 nucleotides.

4. The isolated oligonucleotide of claim 1, wherein the two base deletion is a deletion of GC.

5. The isolated oligonucleotide of claim 1, consisting essentially of the sequence 5′

-GAA CTG AAT AGT CTT CA-3′

(SEQ ID NO;

     4).

14. An isolated oligonucleotide of any one of claims 1, 6, or 9, wherein the oligonucleotide is at least about 14 nucleotides in length.

15. An isolated oligonucleotide of any one of claims 1, 6, or 9, wherein the oligonucleotide is at least about 17 nucleotides in length.

16. An isolated oligonucleotide of any one of claims 1, 6, or 9, wherein the oligonucleotide is at least about 20 nucleotides in length.

17. An isolated oligonucleotide of any one of claims 1, 6, or 9, wherein the oligonucleotide is at least about 23 nucleotides in length.

18. The isolated oligonucleotide of any one of claims 1, 6, or 9, which is labeled.

19. The isolated oligonucleotide of claim 18, wherein the label is selected from the group consisting of a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent label and an enzyme label.

20. A chip array comprising an oligonucleotide selected from any one of claims 1, 6, or 9.

6. An isolated oligonucleotide that specifically hybridizes to a BRCA2 nucleotide sequence, wherein the BRCA2 nucleotide sequence comprises a stop codon beginning at a position corresponding to position 9 of SEQ ID NO:

3, relative to a BRCA2 nucleotide sequence that does not contain the stop codon.

7. The isolated oligonucleotide of claim 6, wherein the stop codon is TAG, TAA or TGA.

8. The isolated oligonucleotide of claim 7, wherein the stop codon is TAG.

9. An isolated oligonucleotide that specifically hybridizes to a BRCA2 nucleotide sequence corresponding to positions 9 to 11 of SEQ ID NO:

3, relative to a BRCA2 nucleotide sequence comprising a two nucleotide deletion corresponding to positions 8 and 9 of SEQ ID NO;

3.

10. The isolated oligonucleotide of claim 9, wherein the two base deletion is a deletion of GC.

11. The isolated oligonucleotide of claim 9, consisting of the sequence 5′

-GAA CTG AGC ATA GTC TT-3′

(SEQ ID NO;

     3).

12. An isolated oligonucleotide consisting of the sequence 5′

-TAC AGC AAG TGG AAA GC (SEQ ID NO;

     1).

13. An isolated oligonucleotide consisting of the sequence 5′

-AAG TTT CAG TTT TAC CAA T-3′

(SEQ ID NO;

     2).