Composition, splice variants and methods relating to ovarian specific genes and proteins

Abstract

The present invention relates to newly identified nucleic acid molecules and polypeptides present in normal and neoplastic ovarian cells, including fragments, variants and derivatives of the nucleic acids and polypeptides. The present invention also relates to antibodies to the polypeptides of the invention, as well as agonists and antagonists of the polypeptides of the invention. The invention also relates to compositions containing the nucleic acid molecules, polypeptides, antibodies, agonists and antagonists of the invention and methods for the use of these compositions. These uses include identifying, diagnosing, monitoring, staging, imaging and treating ovarian cancer and non-cancerous disease states in ovarian, identifying ovarian tissue, monitoring and identifying and / or designing agonists and antagonists of polypeptides of the invention. The uses also include gene therapy, production of transgenic animals and cells, and production of engineered ovarian tissue for treatment and research.

Description

INTRODUCTION [0001] This application claims the benefit of priority from U.S. Provisional Patent Application Ser. No. 60 / 431,321 filed Dec. 6, 2002, U.S. Provisional Patent Application Ser. No. 60 / 431,301 filed Dec. 6, 2002, U.S. Provisional Patent Application Ser. No. 60 / 484,584 filed Jun. 30, 2003 and U.S. Provisional Patent Application Ser. No. 60 / 518,607, filed Nov. 7, 2003 which are herein incorporated by reference in their entireties.FIELD OF THE INVENTION [0002] The present invention relates to newly identified nucleic acids and polypeptides present in normal and neoplastic ovarian cells, including fragments, variants and derivatives of the nucleic acids and polypeptides. The present invention also relates to antibodies to the polypeptides of the invention, as well as agonists and antagonists of the polypeptides of the invention. The invention also relates to compositions comprising the nucleic acids, polypeptides, antibodies, post translational modifications (PTMs), variants...

AI Technical Summary

Problems solved by technology

Unfortunately, women with ovarian cancer are typically asymptomatic until the disease has metastasized.

Reproductive factors have also been associated with an increased or reduced risk of ovarian cancer.

Current screening procedures for ovarian cancer, while of some utility, are quite limited in their diagnostic ability, a problem that is particularly acute at early stages of cancer progression when the disease is typically asymptomatic yet is most readily treatable.

Pelvic examination has failed to yield adequate numbers of early diagnoses, and the other methods are not sufficiently accurate.

Moreover, the CA-125 test is prone to giving false positives in pre-menopausal women and has been reported to be of low predictive value in post-menopausal women.

Although transvaginal ultrasonography is now the preferred procedure for screening for ovarian cancer, it is unable to distinguish reliably between benign and malignant tumors, and also cannot locate primary peritoneal malignancies or ovarian cancer if the ovary size is normal.

While genetic testing for mutations of the BRCA1, BRCA2, hMSH2, and hMLH1 genes is now available, these tests may be too costly for some patients and may also yield false negative or indeterminate results.

While surgical staging is currently the benchmark for assessing the management and treatment of ovarian cancer, it suffers from considerable drawbacks, including the invasiveness of the procedure, the potential for complications, as well as the potential for inaccuracy.

From the foregoing, it is clear that procedures used for detecting, diagnosing, monitoring, staging, prognosticating, and preventing the recurrence of ovarian cancer are of critical importance to the outcome of the patient Moreover, current procedures, while helpful in each of these analyses, are limited by their specificity, sensitivity, invasiveness, and / or their cost.

Although men can get breast cancer, this is extremely rare.

Some detection techniques, such as mammography and biopsy, involve increased discomfort, expense, and / or radiation, and are only prescribed only to patients with an increased risk of breast cancer.

Current methods for predicting or detecting breast cancer risk are not optimal.

While these risk factors are statistically significant, their weak association with breast cancer limited their usefulness.

Current screening methods for detecting cancer, such as breast self exam, ultrasound, and mammography have drawbacks that reduce their effectiveness or prevent their widespread adoption.

Breast self exams, while useful, are unreliable for the detection of breast cancer in the initial stages where the tumor is small and difficult to detect by palpation.

Ultrasound measurements require skilled operators at an increased expense.

There is also the fear of the radiation used in mammography because prior chest radiation is a factor associated with an increase incidence of breast cancer.

At this time, there are no adequate methods of breast cancer prevention.

These markers have problems with limited sensitivity, low correlation, and false negatives which limit their use for initial diagnosis.

For example, while the BRCA1 gene mutation is useful as an indicator of an increased risk for breast cancer, it has limited use in cancer diagnosis because only 6.2% of breast cancers are BRCA1 positive.

However, recent data indicate that less radical procedures may be equally effective, in terms of survival, for early stage breast cancer.

Thus, these patients are better candidates for chemotherapy and radiation therapy with surgery limited to biopsy to permit initial staging or subsequent restaging because cancer is rarely curative at this stage of the disease.

While a number of attempts have been made to classify early stage breast cancer, no consensus recommendation on postoperative radiation treatment has been obtained from these studies.

As discussed above, each of the methods for diagnosing and staging ovarian, and breast cancer is limited by the technology employed.

Images