Compositions and methods for the diagnosis, prevention and treatment of tumor progression

• US 6,025,137 A
• Filed: 09/19/1997
• Issued: 02/15/2000
• Est. Priority Date: 03/29/1995
• Status: Expired due to Term

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Shyjan, Andrew W.
• Primary Examiner(s): Degen, Nancy
• Assistant Examiner(s): SCHWARTZMAN, ROBERT A
• Application Number:
  US08/933,774
• Time in Patent Office: 879 Days
• Field of Search: 435/6, 435/7.1, 536/24.31
• US Class Current: 435/6.14
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• 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: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C12N 15/1034 Isolating an individual clone by screening libraries
• CPC Class Codes: C12N 15/1072 Differential gene expression library synthesis, e.g. subtracted libraries, differential screening

Abstract

The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumor progression in cells involved in human tumors such as melanomas, breast, gastrointestinal, lung, and bone tumors, various types of skin cancers, and other neoplastic conditions such as leukemias and lymphomas. Genes are identified that are differentially expressed in benign (e.g., non-malignant) tumor cells relative to malignant tumor cells exhibiting a high metastatic potential. Genes are also identified via the ability of their gene products to interact with gene products involved in the progression to, and/or aggressiveness of, neoplastic tumor disease states. The genes and gene products identified can be used diagnostically or for therapeutic intervention.

Claims

1. A method for determining whether a fohy030 mRNA is present in a test sample, the method comprising:

a) obtaining a test sample from a test subject;

b) exposing said sample under high stringency conditions to an isolated nucleic acid molecule that hybridizes under high stringency conditions to said fohy030 mRNA; and

c) determining that said fohy030 mRNA is present in said sample when said sample contains mRNA that hybridizes to said isolated nucleic acid molecule,

wherein said fohy030 mRNA is selected from the group consisting of;

i) a mRNA comprising the nucleotide sequence of SEQ ID NO;

8 wherein each T is replaced by U;

ii) a mRNA which encodes the amino acid sequence of SEQ ID NO;

9;

iii) a mRNA which hybridizes under high stringency conditions to the nucleotide sequence of SEQ ID NO;

8, or its complement;

iv) a mRNA which hybridizes under high stringency conditions to the nucleotide sequence of the cDNA insert in ATCC Accession No. 97881; and

v) a mRNA comprising the nucleotide sequence of the cDNA insert contained in ATCC Accession No. 97881 wherein each T is replaced by a U.

2. The method of claim 1, wherein said test sample comprises melanocytes.

3. The method of claim 1, further comprising:

d) obtaining a control sample from a control subject;

e) determining whether said fohy030 mRNA is in said control sample; and

f) determining the amount of said fohy030 mRNA in said test sample relative to said control sample.

4. The method of claim 2, wherein the absence of detectable fohy030 mRNA in said test sample indicates that said test subject has or is at risk of developing metastatic melanoma.

5. The method of claim 3, wherein said test sample comprises melanocytes.

6. The method of claim 5, wherein the absence of detectable fohy030 mRNA in said test sample indicates that said test subject has or is at risk of developing metastatic melanoma.

7. A method for determining the amount of fohy030 mRNA in a test sample relative to a control sample comprising non-metastatic melanoma cells, the method comprising:

a) obtaining a test sample from a test subject;

b) measuring the amount of a fohy030 mRNA in said test sample and in the control sample comprising non-metastatic melanoma cells, wherein said step of measuring comprises exposing said test sample under high stringency conditions to an isolated nucleic acid molecule which hybridizes under high stringency conditions to said fohy030 mRNA; and

c) comparing the amount of fohy030 mRNA in said test sample with the amount of a fohy030 mRNA in said control sample comprising non-metastatic melanoma cells

wherein said fohy030 mRNA is selected from the group consisting of;

i) a mRNA comprising the nucleotide sequence of SEQ ID NO;

8 wherein each T is replaced by U;

ii) a mRNA which encodes the amino acid sequence of SEQ ID NO;

9;

iii) a mRNA which hybridizes under high stringency conditions to the nucleotide sequence of SEQ ID NO;

8;

iv) a mRNA which hybridizes under high stringency conditions to the nucleotide sequence of the cDNA insert in ATCC Accession No. 97881; and

v) a mRNA comprising the nucleotide sequence of the cDNA insert contained in ATCC Accession No. 97881 wherein each T is replaced by a U.

8. The method of claim 7, wherein said test sample comprises melanocytes.

9. The method of claim 8, wherein the presence of a level of fohy030 mRNA in said test sample that is less than the level of fohy030 mRNA in said control sample indicates that said test subject has or is at risk of developing metastatic melanoma.

10. A method for determining whether a fohy030 mRNA is present in a sample comprising melanocytes, the method comprising:

a) obtaining a sample comprising melanocytes from a test subject; and

b) determining whether fohy030 mRNA is present in said sample, said step of determining comprises exposing said test sample under high stringency conditions to an isolated nucleic acid molecule which hybridizes under high stringency conditions to said fohy030 mRNA;

wherein said fohy030 mRNA is selected from the group consisting of;

i) a mRNA comprising the nucleotide sequence of SEQ ID NO;

8 wherein each T is replaced by U;

ii) a mRNA which encodes the amino acid sequence of SEQ ID NO;

9;

iii) a mRNA which hybridizes under high stringency conditions to the nucleotide sequence of SEQ ID NO;

8;

iv) a mRNA which hybridizes under high stringency conditions to the nucleotide sequence of the cDNA insert in ATCC Accession No. 97881; and

v) a mRNA comprising the nucleotide sequence of the cDNA insert contained in ATCC Accession No. 97881 wherein each T is replaced by U.

11. The method of claim 10 wherein the absence of detectable fohy030 mRNA in said sample comprising melanocytes indicates that said test subject has or is at risk of developing metastatic melanoma.

12. The method of claim 10, further comprising:

c) obtaining a control sample comprising melanocytes from a control subject;

d) determining whether said fohy030 mRNA is present in said control sample; and

e) determining the amount of said fohy030 mRNA in said test sample relative to said control sample.

13. The method of claim 12 wherein the absence of detectable fohy030 mRNA in said sample comprising melanocytes indicates that said test subject has or is at risk of developing metastatic melanoma.

14. A method for determining whether a fohy030 encoding DNA present in a test sample contains a mutation, the method comprising:

a) obtaining from a test subject a sample comprising isolated DNA;

b) determining the nucleotide sequence of at least a portion of a fohy030 encoding DNA present in said sample;

c) comparing said sequence determined in step b) with the nucleotide sequence of SEQ ID NO;

8;

wherein a difference between the nucleotide sequence determined in step b) and the nucleotide sequence of SEQ ID NO;

8 indicates that said test sample contains a fohy030 DNA containing a mutation.

15. The method of claim 14, wherein step b) comprises sequencing the entirety of said fohy030 encoding DNA in said sample.