SODD gene expression in cancer

Details SODD gene expression in cancer SODD gene expression in cancer

1999-10-13

2002-04-16

Caputa, Anthony C. (Department: 1621)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

C435S006120, C435S004000, C435S007100, C435S007200, C436S064000, C424S009100

Reexamination Certificate

active

06372444

ABSTRACT:

FIELD OF THE INVENTION
The field of the invention is characterizing tumors by SODD gene copy number and/or expression.
BACKGROUND OF THE INVENTION
The discovery of cancer genes that correspond to the primary genetic alterations driving cancer cell growth and progression can have direct diagnostic and prognostic significance. A clear example of this is in childhood leukemia, where the design of effective therapeutic strategies became dependent upon an accurate molecular diagnosis of translocated cancer genes, once robust tools were developed to examine translocation of cancer genes in clinical samples of childhood leukemias (Table 1).
TABLE 1
Therapeutic implications of the molecular detection of translocated
cancer genes.
Translocation
Leukemia subtype
Recommended treatment
TEL-AML
Pro-B cell
Antimetabolites
a
Pre-B cell
Genotoxic drugs and antimetabolites
Ig-MYC
B-cell
Genotoxic drugs and antimetabolites
BCR-ABL
Pro-B cell
Allogeneic stem cell transplantation
AML1-ETO
Myeloid-M2
Intensive chemotherapy (cytarabine)
CBF&bgr;-MYH11
Myeloid-M4
Intensive chemotherapy (cytarabine)
PML-RARa
Myeloid-M3
Retinoic acid and chemotherapy
In solid tumors such as breast cancer, two of the most promising prognostic markers are the p53 and HER2 cancer genes, both of which underlie common primary genetic alterations (Kovach et al., 1996, Proc. Natl. Acad. Sci. USA 93, 1093-1096; Hartmann et al., 1997, Trends Genet. 13, 27-33; Thor et al., 1998, J. Natl. Cancer Inst. 90, 1346-1360; Ross and Fletcher, 1998, Oncologist 3, 237-252), however it would be useful to develop more prognostic markers that correspond to primary genetic alterations.
Gene amplification is one of the primary mutational mechanisms for causing primary genetic alterations in solid tumors, and most of the chromosomal regions that undergo amplification are not well characterized and do not harbor known oncogenes. Discovery of these amplified cancer genes will provide novel targets for diagnostic development. Over 20 high-level amplified regions in breast cancers have been identified by CGH, but only three have been firmly associated with established oncogenes (HER2 at 17q12-q21, MYC at 8q24, and BCL1/Cyclin D1 at 11q13) (Knuutila et al., 1998, Am. J. Pathol. 152, 1107-1123).
By representational difference analysis (RDA) (Lisitsyn et al. 1995, Proc. Natl. Acad. Sci. USA 92, 151-155) of a human breast cancer biopsy, we discovered a RDA probe that mapped to 8p11 and that detected amplification in several breast cancer samples. Amplification of 8p11 is associated with amplification of FGFR1, although not all tumors amplified for FGFR1 overexpress the gene (Dib et al., 1995, Oncogene 10, 995-1001; Ugoline et al., 1999, Oncogene, 18, 1903-1910). Our results indicate that FGFR1 is not the only oncogene that is driving amplification of this region. For one, the cell line BT483 is not amplified for FGFR1 but amplified for the RDA probe. Second, one tumor (89-249) analyzed by quantitative RT-PCR did not have the FGFR1 gene overexpressed, which rules out FGFR1 as the oncogene responsible for amplification of the region in this tumor. Third, the physical map of this region revealed FGFR1 is ~0.6 Mb away from the RDA probe and there are sequences in between the RDA probe and FGFR1 that are not amplified or less amplified than the RDA probe and FGFR1. Thus the region amplified near the RDA probe contains a separate oncogene.
Based on more detailed analysis of these primary tumors, and analysis of additional amplified primary tumors, the smallest area of common overlap of amplification encompasses inter alia, SODD (originally coined from the acronym of “Suppressor of Death Domains”), a protein that binds to the TNF-receptor's death domain and that inhibits TNF-induced apoptosis (Jiang et al., 1999, Science 283, 543-546 and copending application Ser. No. 09/035,676, filed: Mar. 05, 1998).
SUMMARY OF THE INVENTION
The invention provides methods and compositions for diagnosing and treating tumors. In particular embodiments, the invention provides methods for characterizing tumors for SODD gene copy number and/or expression and for using this diagnosis in guiding treatment options. Accordingly, the invention provides methods for biasing therapeutic options by (a) contacting a biopsy of a tumor with an agent which specifically binds a SODD gene or SODD gene product thereof; (b) measuring specific binding of the agent to the SODD gene or gene product to determine an amount of the SODD gene or gene product present in the biopsy; and (c) biasing therapeutic options for treating the tumor based on the amount of the SODD gene or gene product present in the biopsy. The target may be a SODD gene, transcript (e.g. mRNA or cDNA), or translate (i.e. SODD polypeptide). SODD genes and transcripts are generally detected with specific hybridization probes, including PCR primers and translates are generally detected with SODD protein-specific binding agents, including SODD binding proteins like antibodies and TNF receptor domains. The amount of SODD gene or gene expression product in the tumor biopsy is used to guide treatment. For example, a relatively elevated amount of the SODD gene or gene product present in the biopsy can reduce the indicability or advisability of radiation therapy for treating the tumor.


REFERENCES:
patent: 5912143 (1999-06-01), Bandman et al.
patent: 6107088 (2000-08-01), Korneluk et al.
Gallo et al. Int. J. Cancer (Pred. Oncol.) 84, 573-579 (1999).

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