Method for early diagnosis of, and determination of prognosis in, cancer

• US 6,576,420 B1
• Filed: 06/17/1999
• Issued: 06/10/2003
• Est. Priority Date: 06/23/1998
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology, Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Carrera, Carlos J., Schmid, Mathias, Carson, Dennis A.
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): MAUPIN, CHRISTINE L
• Application Number:
  US09/335,231
• Time in Patent Office: 1,454 Days
• Field of Search: 435/6, 435/91.2, 435/7.92, 536/23.1, 536/23.2, 536/24.1, 536/24.2, 536/24.3, 536/24.33
• US Class Current: 435/6.11
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification

Abstract

The invention provides a method for diagnosis of, and determining a prognosis for, cancer causatively associated with derangements of chromosome 9p21. Underlying the invention is the discovery that such derangements have their genesis in deletions occurring centromeric to STS 3.21, most often including breakpoints in exon 8 and/or between exons 4 and 5 of the gene which codes for methylthioadenosine phosphorylase. As the cancer and tumor development advance, deletions in 9p21 progress centromerically from the genesis point toward the gene encoding p16. Thus, the method of the invention is performed by determining whether (a) portions of the 9p21 region including and telomeric to STS 3.21 are deleted; and (b) portions of the 9p21 region centromeric to STS 3.21 are deleted; wherein a positive finding in step (a) and a negative finding in step(b) are indicative of a cancer in an early stage of tumor development and a positive finding in step (b) is indicative of a cancer in an advanced stage of tumor development.

Claims

1. A method for diagnosis or prognosis for cancer associated with deletions of chromosome 9p21, the method comprising:

(a) determining whether any portion of the 9p21 chromosome including and telomeric to sequence tagged site 3.21 is deleted; and

,

(b) determining whether any portion of the 9p21 chromosome centromeric to sequence tagged site 3.21 is deleted;

wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer at an early stage and, wherein a positive finding in step (a) and a positive finding in step (b) are indicative of a cancer at an advanced stage, thereby determining a diagnosis or prognosis for cancer.

2. The method according to claim 1, further comprising the use in step (a) of primer pairs selected from the group of oligonucleotides consisting of SEQ ID NOS:

3 and 4, SEQ ID NOS;

21 and 22 and SEQ ID NOS;

23 and 24.

3. The method according to claim 1, further comprising the use in step (b) of primer pairs selected from the group of oligonucleotides consisting of SEQ ID NOS:

5 and 6, SEQ ID NOS;

7 and 8, SEQ ID NOS;

9 and 10, SEQ ID NOS;

11 and 12, SEQ ID NOS;

13 and 14, SEQ ID NOS;

15 and 16 and SEQ ID NOS;

17 and 18.

4. The method according to claim 1, further comprising the use of the primer pair of SEQ ID NOS:

1 and 2 as a control for step (a).

5. The method according to claim 1, wherein the cancer is a glioma.

6. The method according to claim 1, wherein the cancer is a primary lymphoid malignancy.

7. The method according to claim 1, wherein the cancer is non-small cell lung cancer.

8. The method according to claim 1, wherein the cancer is a melanoma.

9. A method for diagnosis or prognosis for cancer associated with deletions of chromosome 9p21, the method comprising:

(a) determining whether any portion of the gene encoding metabolic enzyme mehylthioadenosine phosphphorylase is deleted; and

,

(b) determining whether any portion of the 9p21 chromosome centromeric to sequence tagged site 3.21 is deleted;

wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer at an early stage and, wherein a positive finding in step (a) and a positive finding in step (b) are indicative of a cancer at an advanced stage, thereby determining a diagnosis or prognosis for cancer.

10. The method according to claim 9 wherein step (a) comprises determining whether exon 8 of the gene coding for metabolic enzyme mehylthioadenosine phosphphorylase is deleted.

11. The method according to claim 9 wherein step (a) comprises determining whether the region from exon 4 to exon 5 of the gene coding for metabolic enzyme mehylthioadenosine phosphphorylase is deleted.

12. The method according to claim 9 wherein step (b) comprises determining whether any portion of the gene coding for p16INK4A is deleted.

13. The method according to claim 9, further comprising the use in step (a) of primer pairs selected from the group of oligonucleotides consisting of SEQ ID NOS:

3 and 4, SEQ ID NOS;

21 and 22 and SEQ ID NOS;

23 and 24.

14. The method according to claim 9, further comprising the use in step (b) of primer pairs selected from the group of oligonucleotides consisting of SEQ ID NOS:

5 and 6, SEQ ID NOS;

7 and 8, SEQ ID NOS;

9 and 10, SEQ ID NOS;

11 and 12, SEQ ID NOS;

13 and 14, SEQ ID NOS;

15 and 16 and SEQ ID NOS;

17 and 18.

15. The method according to claim 9, further comprising the use of the primer pair of SEQ ID NOS:

1 and 2 as a control for step (a).

16. The method according to claim 9, wherein the cancer is a glioma.

17. The method according to claim 9, wherein the cancer is a primary lymphoid malignancy.

18. The method according to claim 9, wherein the cancer is non-small cell lung cancer.

19. The method according to claim 9, wherein the cancer is a melanoma.

20. A method for diagnosis of, and determining a prognosis for, cancer causatively associated with derangements of chromosome 9p21, the method comprising:

(a) determining whether any portion of the gene encoding metabolic enzyme mehylthioadenosine phosphphorylase is deleted; and

,

(b) determining whether any portion of the gene coding for p16INK4A is deleted;

wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer at an early stage and, wherein a positive finding in step (a) and a positive finding in step (b) are indicative of a cancer at an advanced stage, thereby determining a diagnosis or prognosis for cancer.

21. The method according to claim 20, further comprising the use in step (a) of primer pairs selected from the group of oligonucleotides consisting of SEQ ID NOS:

3 and 4, SEQ ID NOS;

21 and 22 and SEQ ID NOS;

23 and 24.

22. The method according to claim 20 further comprising the use in step (b) of primer pairs selected from the group of oligonucleotides consisting of SEQ ID NOS:

5 and 6, SEQ ID NOS;

7 and 8, SEQ ID NOS;

9 and 10, SEQ ID NOS;

11 and 12, SEQ ID NOS;

13 and 14, SEQ ID NOS;

15 and 16 and SEQ ID NOS;

17 and 18.

23. The method according to claim 20, further comprising the use of the primer pair of SEQ ID NOS:

1 and 2 as a control for step (a).

24. The method according to claim 20, wherein the cancer is a glioma.

25. The method according to claim 20, wherein the cancer is a primary lymphoid malignancy.

26. The method according to claim 20, wherein the cancer is non-small cell lung cancer.

27. The method according to claim 20, wherein the cancer is a melanoma.