Profiling tumor specific markers for the diagnosis and treatment of neoplastic disease

• US 20070161023A1
• Filed: 11/30/2006
• Published: 07/12/2007
• Est. Priority Date: 11/16/2000
• Status: Active Grant

• Current Assignee: Spinal Cord Society/Cedars-Sinai Medical Center
• Original Assignee: Spinal Cord Society/Cedars-Sinai Medical Center
• Inventors: Palm, Kaia
• Granted Patent: US 7,812,124 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• 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: G01N 33/574 for cancer

Abstract

A method of diagnosing cancer comprising the identification of neoplastic molecular markers is disclosed. Tumor-related or neoplastic molecular markers are identified from samples taken from a subject and the molecular profile of those markers is determined. Based upon the neoplastic molecular marker profile of the subject, the tumor sub-type is ascertained and an appropriate treatment protocols initiated.

Claims

1. A method for determining the presence of neoplastic molecular markers in a host comprising:

a) obtaining a test sample from the host;

b) identifying the presence of neoplastic molecular markers in the test sample using an array of neoplastic molecular marker specific reagents; and

c) analyzing the array of neoplastic disease molecular marker specific reagents,

wherein the analysis yields the identification of a neoplastic disease from which the neoplastic molecular markers originate.

2. The method of claim 1, wherein the neoplastic disease is lung cancer.

3. The method of claim 1, wherein the neoplastic disease is prostate cancer.

4. The method of claim 1, wherein the neoplastic disease is astrocytoma.

5. The method of claim 1, wherein the neoplastic disease is neuroblastoma.

6. The method of claim 1, wherein the array of neoplastic molecular marker specific reagents is used in an immunological assay method.

7. The method of claim 4, wherein the immunological assay method is selected from the group consisting of dot blot analysis, slot blot analysis, and ELISA.

8. The method of claim 1, wherein the expression pattern of the array of neoplastic molecular markers is determined by evaluating the quantity of RNA or DNA encoding said markers.

9. The method of claim 8, wherein the quantity of RNA or DNA is determined by a method selected from the group consisting of Northern blot analysis, Southern blot analysis, Western blot analysis, RT-PCR, PCR, nucleic acid sequence based amplification assays (NASBA), transcription mediated amplification (TMA), or computerized detection matrix.

12. The array of claim 8, wherein the reagents comprise reagents specific for the detection of NeuroD2, ATH5, Sox1, Sox2, and LMO4.

10. An array for identifying a neoplastic source sample, comprising a plurality of neoplastic molecular markers arranged in an assayable format, said molecular markers being differentially expressed as compared to a comparable non-neoplastic source sample.

11. The array of claim 10, wherein the array comprises neoplastic molecular marker specific reagents to detect the presence of a small cell lung cancer.

13. The array of claim 10, wherein the array comprises of neoplastic molecular marker specific reagents to detect the presence of a non-small cell lung cancer.

14. The array of claim 13, wherein the reagents comprise reagents specific for the detection of Groucho1, SOX2, SOX3 and NKX5.2.

15. The array of claim 13, wherein the reagents comprise reagents specific for the detection of Zic family members.

16. The array of claim 15, wherein the reagents comprise reagents specific for the detection of MyT-2, Hes-5, and SMAD6.

17. The array of claim 10, wherein the reagents comprise reagents specific for the detection of neuronal genes are selected from the group consisting of Neurogenin-1/MATH4c, Neurogenin-2/MATH4a, Neurogenin-3/MATH4b, Emx-1, Emx-2, Isl1, Lhx2, Lhx3, Lhx4, Lhx5, Lhx6, Lhx7, Lhx9, LMO1, LMO2, LMO4, HES1, HES2, HES3, HES4, HES5, HES6, HES7, or combinations thereof.

18. The array of claim 10, wherein the reagents comprise reagents specific for HES1, HES2, HES3, HES4, HES5, HES6, HES7, SMAD1, SMAD2, SMAD3, SMAD4, SAMD5, SMAD6, SMAD7, SMAD8, SMAD9, SMAD10, or combinations thereof.

19. The array of claim 10, wherein the reagents comprise reagents specific for HES1, HES2, HES3, HES4, HES5, HES6, HES7, Emx-1, Emx-2, Isl1, Lhx2, Lhx3, Lhx4, Lhx5, Lhx6, Lhx7, Lhx9, NeuroD1, NeuroD2, NeuroD3, ASH-1/MASH1, ASH-2/MASH2, ASCL-3/reserved, or combinations thereof.

20. The array of claim 10, wherein the array comprises neoplastic molecular marker specific reagents indicative of a prostate cancer.

21. The array of claim 20, wherein the neoplastic molecular marker specific reagents are indicative of prostate cancer of Group I.

22. The array of claim 21, wherein the reagents comprise reagents specific for the detection of NeuroD2, ATH1, Isl1, LMO4, and GBX2.

23. The array of claim 20, wherein the neoplastic molecular marker specific reagents are indicative of prostate cancer of Group II.

24. The array of claim 23, wherein the reagents comprise reagents specific for the detection of Nkx2.2, Sal11, and Sharp1.

25. The array of claim 10, wherein the array comprises neoplastic molecular marker specific reagents are indicative of an astrocytoma.

26. The array of claim 25, wherein the neoplastic molecular marker specific reagents are indicative of a subclass I astrocytoma.

27. The array of claim 26, wherein the reagents comprise reagents specific for the detection of negative regulators of neural differentiation markers and neuronal genes.

28. The array of claim 27, wherein the negative regulators of neural differentiation markers are selected from the group consisting of Msx-1, Msx-2, or combinations thereof.

29. The array of claim 27, wherein the neuronal genes are selected from the group consisting of Neurogenin-1/MATH4c, Neurogenin-2/MATH4a, Neurogenin-3/MATH4b, Emx-1, Emx-2, Isl1 Lhx2, Lhx3, Lhx4, Lhx5, Lhx6, Lhx7, Lhx9, LMO10, LMO2, LMO4, HES1, HES2, HES3, HES4, HES5, HES6, HES7, or combinations thereof.

30. The array of claim 26, wherein the reagents comprise reagents specific for HES1, HES2, HES3, HES4, HES5, HES6, HES7, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, SMAD7, SMAD8, SMAD9, SMAD10, or combinations thereof.

31. The array of claim 26, wherein the array comprises high expression of HES genes and neural genes of Neurogenin, NeuroD and ASH family.

32. The array of claim 26, wherein the reagents comprise reagents specific for HES1, HES2, HES3, HES4, HES5, HES6, HES7, Emx-1, Emx-2, Isl1, Lhx2, Lhx3, Lhx4, Lhx5, Lhx6, Lhx7, Lhx9, NeuroD1, NeuroD2, NeuroD3, ASH-1/MASH1, ASH-2/MASH2, ASCL-3/reserved, or combinations thereof.

33-66. -66. (canceled)