Unmet Need:
Papillary thyroid cancer (PTC) is the most common thyroid cancer, accounting for about 80% of thyroid malignancies. Although PTC is usually indolent and curable with surgical thyroidectomy followed by radioiodine treatment, many patients do have recurrence and some become incurable and will die from the disease. Consequently, it is important to undertake appropriate risk stratification and prognostic evaluation for patients with PTC in order to provide optimal clinical management of the cancer. There is a need for improved and/or additional means for detecting, diagnosing, categorizing, treating, and predicting outcomes for thyroid cancers.
Technical Overview:
The BRAF gene was found to be activated by mutation in human cancers, predominantly in malignant melanoma. JHU researchers tested a large number of primary tumors by PCR amplifications of BRAF exon 15 followed by restriction enzyme analysis and found a 68% frequency of a missense T to A transversion at nucleotide 1796 in papillary thyroid carcinoma. This mutation provides a basis for novel diagnostic and therapeutic applications in thyroid cancer
PROBLEM SOLVED
With the demonstration of the oncogenic effect of the BRAF T1796A transversion mutation, it is conceivable that BRAF mutation plays an important tumorigenic role in PTC and may thus affect the clinicopathologic outcomes of these cancers. T1796A mutations of the BRAF gene have been determined to be common in thyroid carcinomas and can be used to distinguish between benign and malignant carcinomas. The inventors have also discovered that the presence of the mutation indicates a higher level of recurrence for PTC.
Stage of Development:
Preclinical
· The inventors have successfully demonstrated that BRAF mutation is associated with a number of pathologic features of PTC that are known to be predictors for a poor prognosis.
· The inventors have further shown that BRAF mutation is associated with a higher incidence of tumor recurrence.
· Preoperative examination of BRAF mutation on fine needle aspiration specimens was demonstrated to be a reliable and sensitive method to detect BRAF mutation.
Publication(s):
1. NCI J Natl Cancer Inst (2003) 95 (8): 625-627
2. JAMA. 2013 Apr 10;309(14):1493-501.
3. J Clin Endocrinol Metab. 2005 Dec;90(12):6373-9.
4. J Clin Endocrinol Metab. 2004 Jun;89(6):2867-72.
5. J Clin Endocrinol Metab. 2007 Dec;92(12):4712-8.
6. J Clin Oncol. 2015 Jan 1;33(1):42-50.
7. J Clin Oncol. 2014 Sep 1;32(25):2718-26.
8. Endocrine Rev. 2007 Dec (1): 742-762
9. Ann Surg. 2007 246(3): 466–471
10. US 7,378,233
11. US 7,923,460
