Invented by Thomas Giordano, Ronald Koenig, Rork Kuick, Samir Hanish, Dafydd G. Thomas, Yuri Nikiforov, University of Cincinnati
The University of Cincinnati invention works as follows
The invention concerns compositions and methods that can be used to diagnose cancer, including, but not limited, to identify cancer markers. The present invention provides gene expression profiles that are associated with thyroid cancers. The methods of the invention identify genes that can be used to diagnose and characterize thyroid cancer. The genes can also be used as targets for therapeutic and drug screenings in cancer.Background for Expression profile for thyroid cancer
There are four types of thyroid cancer: papillary carcinoma (PC), follicular carcinoma (Medullary), and anaplastic. Papillary carcinoma (PC), which accounts for up to 80% in malignant thyroid tumors, is the most prevalent type of thyroid cancer (Hundahl and colleagues, 1998).
Radiation to the neck and head during childhood or infancy is associated with a higher risk of developing thyroid cancer. It can develop as soon as five years after radiation exposure, or as late as 20 years later. Thyroid cancer can also be linked to goiter and a family history.
The type of thyroid cancer and whether it has spread beyond the thyroid are all factors that affect the prognosis. Patients younger than 40 years old who have not had cancer spread beyond their thyroid are better off.
The majority (but not all) of these PCs are not life-threatening and can be treated with radioactive iodine ablation followed by thyroidectomy (DeGroot, 1990). A small percentage of PCs will recur, which can cause serious morbidity (Hundahl and colleagues, 1998; LiVolsi 1996). A smaller number of PCs progress from well-differentiated to poorly- or undifferentiated cancer, which is associated with a marked decrease in survival rates (Giuffrida & Gharib 2000). Improved methods are required to detect and treat thyroid cancer early.
The invention concerns compositions and methods that can be used to diagnose cancer, including, but not limited, to identify cancer markers. The present invention includes gene expression profiles that are associated with thyroid cancers. The invention also provides novel markers that can be used to diagnose, characterize, and treat thyroid cancers.
Accordingly, the present invention provides diagnostic tools and kits for diagnosing, characterizing, and treating thyroid cancer in certain embodiments (e.g. into sub-types). This invention also provides methods for screening compounds that modify cancer marker expression and function. They are useful in thyroid cancer therapy.
For example, the present invention offers a method of characterizing thyroid tissue. It involves obtaining a thyroid tissue sample from the subject and then detecting the level kallikrein 10. The detection of the expression level of kallikrein10 in a sample is possible according to some embodiments. This can be done by either exposing the mRNA of the subject to a nucleic acids probe that complements the mRNA, or performing a QRT-PCR assay. In other embodiments, the detecting the detecting the level of expression of kallikrein 10 comprises detecting the level of expression of a kallikrein 10 polypeptide (e.g., by exposing the polypeptide to an antibody specific to the polypeptide and detecting the binding of the antibody to the polypeptide (e.g., using immunohistochemistry).
In some cases, a higher level of expression for the kallikrein10 gene than the non-cancerous controls is indicative of thyroid carcinoma in the sample. In some embodiments, the subject is a human subject. The sample may contain tumor tissue in certain embodiments. The characterization of the thyroid tissue may include identifying the type of thyroid cancer within the tissue. The method may also include the step of giving a prognosis (e.g., whether there is a risk of developing thyroid carcinoma or metastatic thyroid cancer). Other embodiments include the step of diagnosing the subject (e.g., thyroid cancer diagnosis or type of thyroid carcinoma).
The present invention also provides a kit for characterizing the thyroid cancer of a subject. It includes: a reagent capable specifically of detecting the expression of Kallikrein 10, such as a nucleic acids probe or an antibody specific for a Kallikrein10 mRNA or protein; and instructions for how to use the kit to characterize the thyroid cancer. Some embodiments include instructions that the United States Food and Drug Administration requires for in vitro diagnostic products.
The present invention also provides a method for screening compounds. It involves providing a thyroid sample and one or more test chemicals. Then, contacting the sample with the test compounds and detecting any change in expression of Kallikrein 10 in that sample. In some cases, the cell may be in vitro or in-vivo.
The present invention also provides a therapeutic agent to treat thyroid cancer. In some embodiments, the therapeutic agents target a specific cancer marker. Other embodiments use a kinase inhibitor (e.g. gleevac, BAY 43-9006).
The present invention also provides a method of characterizing thyroid tissue. This involves taking a sample of thyroid tissue from a subject and then detecting the level expression of claudin 1. Papillary carcinoma can be identified in some cases by an increase in expression of the Claudin 1 gene relative the level of expression in a non-cancerous sample.
The present invention also provides a method of characterizing thyroid tissue. This involves taking a sample of thyroid tissue from a subject and determining the expression of one or more genes, including but not limited to ARNTL, CHST2, CITED1, CLDN1, CLDN16 and CTSH. Some embodiments indicate that papillary thyroid carcinoma is caused by an altered expression of one or more genes relative to normal thyroid levels.
The present invention also provides a method of characterizing thyroid tissue. This includes obtaining a thyroid tissue sample from a subject and determining the level of expression for one or more of PPARG or ATP10B or C6orf29, CHIA or CNR1, ANGPTL4, TFPI2, MFAP3L or IGFBP2, FBP1, FBN2, LEPREL1, TNFRSF21 or MYOZ1, ANKS1, GENX-3414 or SSX1, SSX3, SSX3, SSX5, C7orf32 or EPHB1, CHST5, CHST5, C7orf32 or C7orf32, a, or C7orf32, a, a, a, a, a, a, a,, a, a, a, a, a, a,,, a, PT1A1A1, PL2, a, a, p1, PT1, a, ping1, a, a,, pon1, or EPHB1, s5, a, a, PT1, a, d5, a, a, a, a, a, a, s, a,, a, a, if32,,,, a, a, en Some embodiments indicate that a subject has follicular cancer by altering the expression of one or more genes relative to normal thyroid levels.
DESCRIPTION OFF THE FIGURES
FIG. FIG. 1A and 2B show the principal component analysis of expression profiling and morphology data, as well as mutational status.
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FIG. “FIG. follicular carcinomas, follicular adenomas and normal thyroids.
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