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Tert and braf mutations in human cancer

A technology for patients and thyroid cancer, applied in the direction of biochemical equipment and methods, microbiological determination/inspection, medical preparations containing active ingredients, etc.

Inactive Publication Date: 2016-11-23
迈克明照邢
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the molecular mechanisms, especially the genetic background, of this particular PTC patient population need to be better defined

Method used

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  • Tert and braf mutations in human cancer
  • Tert and braf mutations in human cancer
  • Tert and braf mutations in human cancer

Examples

Experimental program
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Effect test

example 1

[0086] Example 1: Coexisting BRAF V600E and TERT promoter mutations are a unique genetic background that predicts and marks invasion The most vicious human cancer.

[0087] Purpose : To investigate the prognostic value of BRAF V600E mutation and TERT promoter mutation CHR5:1,295,228C>T (C228T) alone and in combination in papillary thyroid carcinoma (PTC).

[0088] patients and methods : A retrospective study of the relationship between the clinicopathological findings of BRAF and TERTC228T mutations in 507 cases (365 women and 142 men) of PTC, aged 45.9±14.0 years and 24 months (quartile 8-78 months, median follow-up).

[0089] result Coexisting BRAF V600E and TERT C228T mutations are more associated with high-risk clinicopathological features of PTC than either mutation. Tumor recurrence was 25.8% (50 / 194) [77.60 (95% CI 58.81-102.38) per 1000 person-years] and [22.88 (95% CI 16.00-32.72) per 1000 person-years] in BRAF 9.6% mutation-positive versus [ 108.55 (95% CI...

Embodiment 2

[0124] Example 2: Two gene mutations coexist in melanocytoma—TERTC228 / 250T promoter mutation and BRAF Significant association between V600E mutations.

[0125] Table 8. Association of TERTC228 / 250T and BRAFV600E mutations in melanocytoma

[0126]

[0127] In Tables 9 to 11: "0" means no event occurred; "1" means event occurred.

[0128] In the analysis in Table 9 below, patients were divided into two groups: one, BRAF wild type (non-mutated); two, BRAF mutated. Compared with group 1, the death rate of group 2 was slightly and significantly increased, indicating that BRAF mutation has a slightly significant predictive ability for the death of melanoma patients. "1" means the patient died, and "0" means no death.

[0129] Table 9. Role of BRAF mutations in death in melanoma patients

[0130]

[0131] In the analysis in Table 10 below, patients were divided into two groups: one, positive (1) for TERT C228T / C250T mutation; two, negative (0) for wild-type TERT. The mo...

example 3

[0137] Example 3: Application of TERT promoter mutation in the diagnosis of thyroid fine needle aspiration

[0138] Thyroid cancer is a common endocrine malignancy, and its incidence has rapidly increased globally in recent years (Howlader et al. 2014; Jemal et al. 2011). In the United States, there were 62980 new cases of thyroid cancer and an estimated 1890 deaths from this cancer in 2014 (Howlader et al., 2014). Diagnosis of thyroid cancer usually begins with the evaluation of thyroid nodules, which are very common and visible in about 5-10% of adults over the age of 60 years and over 50-70% of people over the age of 60 (Guth, et al. 2009; Mazzaferri 1993). Therefore, the clinical evaluation of thyroid nodular malignancy is a major task in thyroid practice where the main method of diagnosis is fine needle aspiration biopsy (FNAB). Fine needle aspiration (FNAB) is accurate in most patients because it can provide a reliable diagnosis of benign or malignant thyroid tumors ...

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Abstract

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions related to certain mutations in cancer.In one embodiment, a method for treating a subject having aggressive thyroid cancer comprises the steps of (a) obtaining a biological sample from the subject; (b) performing an assay on the sample obtained from the subject to identify a mutation at 1 295 228 C>T (C228T), corresponding to -124 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene, and a T1799A mutation in the BRAF gene that results in a V600E amino acid change; (c) identifying the subject as having or likely to develop aggressive thyroid cancer if the C228T and V600E mutations are identified; and (d) treating the subject with one or more treatment modalities appropriate for a subject having or likely to develop aggressive thyroid cancer. Similar approaches are applied to other human cancers harboring both BRAF V600E mutation and TERT promoter mutations.

Description

[0001] Cross reference to related applications [0002] This application claims rights and interests from U.S. Provisional Application No. 62 / 0349668 filed August 2014, U.S. Provisional Application No. 61 / 976109 filed April 7, 2014, and April 2014 Patent application No. 61 / 973584 filed on the 1st. Each of these is hereby incorporated by reference in its entirety. [0003] Statement of Government Interest [0004] This invention was supported by US Government Research Grant Nos. R01CA134225 and R01CA113507 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0005] The present invention relates to the field of cancer. More specifically, the invention provides methods and compositions related to certain cancer mutations. [0006] Consolidation of electronically submitted material by index [0007] The application consists of a sequence of listings, which have been submitted electronically via the EFS-Web site,...

Claims

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Application Information

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IPC IPC(8): C12Q1/68A61K31/00A61K38/00A61K39/00A61P35/00
CPCA61K31/4184A61K31/437A61K31/44A61K31/506A61K31/519A61K38/1709A61P35/00C12Q1/6886C12Q2600/112C12Q2600/156A61K2300/00
Inventor 迈克尔·刑
Owner 迈克明照邢
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