DLC-1 gene deleted in cancers

• US 20050106616A1
• Filed: 11/24/2004
• Published: 05/19/2005
• Est. Priority Date: 02/25/1998
• Status: Active Grant

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: The United States of America As Represented By The Secretary of Agriculture
• Inventors: Thorgeirsson, Snorri S., Yuan, Bao-Zhu, Popescu, Nicholas
• Granted Patent: US 7,534,565 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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

Abstract

A cDNA molecule corresponding to a newly discovered human gene is disclosed. The new gene, which is frequently deleted in liver cancer cells and cell lines, is called the DLC-1 gene. Because the gene is frequently deleted in liver cancer cells, but present in normal cells, it is thought to act as a tumor suppressor. This gene is also frequently deleted in breast and colon cancers, and its expression is decreased or undetectable in many prostate and colon cancers. Also disclosed is the amino acid sequence of the protein encoded by the DLC-1 gene. Methods of using these biological materials in the diagnosis and treatment of hepatocellular cancer, breast cancer, colon cancer, prostate cancer, and adenocarcinomas are presented.

Claims

1. A method for diagnosing a cancer in a subject, comprising detecting decreased expression of a nucleic acid encoding SEQ ID NO:

2 in a sample from the subject, wherein detection of decreased expression of the nucleic acid encoding SEQ ID NO;

2 diagnoses the cancer.

2. The method of claim 1, wherein the cancer is breast cancer.

3. The method of claim 1, wherein the cancer is liver cancer.

4. The method of claim 1, wherein the cancer is colorectal cancer.

5. The method of claim 1, wherein the cancer is prostate cancer.

6. The method of claim 1, wherein the sample is a peripheral blood, a urine, a saliva, a tissue biopsy, a surgical specimen, or an autopsy sample.

7. The method of claim 1, wherein the detection of decreased expression of a nucleic acid encoding SEQ ID NO:

2 is by an amplification reaction, a hybridization reaction, or a change in electrophoretic mobility.

8. The method of claim 7, wherein the detection of decreased expression of a nucleic acid encoding SEQ ID NO:

2 is by amplification reaction, and the amplification reaction is polymerase chain reaction.

9. The method of claim 1, wherein the sample is a tissue biopsy, a surgical specimen, or an autopsy sample.

10. The method of claim 1, wherein the detection of decreased expression of a nucleic acid encoding SEQ ID NO:

2 comprises detecting decreased levels of a mRNA encoding SEQ ID NO;

2 in a sample from the subject.

11. The method of claim 1, wherein the detection of decreased expression of a nucleic acid encoding SEQ ID NO:

2 comprises detecting a deletion in a nucleic acid encoding SEQ ID NO;

2 in a sample from the subject.

12. A method for diagnosing a cancer in a subject, comprising detecting decreased expression of a polypeptide at least 95% identical to SEQ ID NO:

2 in a sample from the subject, wherein detection of decreased expression of the polypeptide at least 95% identical to SEQ ID NO;

2 diagnoses the cancer.

13. The method of claim 12, wherein the cancer is breast cancer.

14. The method of claim 12, wherein the cancer is liver cancer.

15. The method of claim 12, wherein the cancer is colorectal cancer.

16. The method of claim 12, wherein the cancer is prostate cancer.

17. The method of claim 12, wherein the sample is a peripheral blood, a urine, a saliva, a tissue biopsy, a surgical specimen, or an autopsy sample.

18. The method of claim 12, comprising

(a) incubating an antibody that specifically binds to the polypeptide with the sample from the subject under conditions such that the antibody will specifically bind to the polypeptide present in the sample to form an antibody:

polypeptide complex;

(b) quantifying the amount of the antibody;

polypeptide complex; and

(c) comparing the amount of the antibody;

polypeptide complex in the sample with the amount of antibody;

polypeptide complex in normal subject cells, wherein a difference in the amount of the antibody;

polypeptide complex in the sample diagnoses the cancer.

19. The method of claim 12, wherein the sample is a tissue biopsy, a surgical specimen, or an autopsy sample.