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CN-122012703-A - Gene polymorphism site related to thyroid cancer and application thereof

CN122012703ACN 122012703 ACN122012703 ACN 122012703ACN-122012703-A

Abstract

The invention provides somatic mutation sites of thyroid cancer pathogenesis pathogenic genes and application thereof, in particular to a group of mutation sites of thyroid cancer pathogenesis pathogenic genes, including GNAS gene mutation sites, NRAS gene mutation sites, TSHR gene mutation sites and the like.

Inventors

  • SONG HUAIGUANG
  • LIU LEI

Assignees

  • 上海安甲生物科技有限公司

Dates

Publication Date
20260512
Application Date
20170606

Claims (10)

  1. 1. Use of a gene mutation site of group (I) or a detection reagent thereof for the preparation of a reagent or kit for identifying benign and malignant thyroid nodules, said group (I) comprising the following gene mutation sites: GNAS gene: NM_016592:exon1:c.C205A; TSHR gene: NM_000369:exon10:c.A2252G; BRAF gene: NM_004333:exon15:c.T1799A。
  2. 2. The use according to claim 1, wherein said group (I) further comprises the following gene mutation sites: GNAS gene: NM_016592:exon1:c.C216T, and/or The group (I) further comprises the following gene mutation sites: TSHR gene: NM-000369: exon10: c.A2098G, and/or The group (I) further comprises the following gene mutation sites: BRAF gene: NM_004333:exon11:c.G1338A。
  3. 3. the use of claim 1, wherein the reagent comprises a primer, a probe, a chip, or an antibody.
  4. 4. The method of claim 1, wherein the subject comprises a human or non-human mammal.
  5. 5. The use according to claim 1, wherein the kit contains one or more reagents selected from the group consisting of: (A) Specific primers for gene detection; (B) A specific probe for gene detection; (C) A chip for gene detection; (D) A specific antibody for detecting an amino acid mutation corresponding to a mutated gene.
  6. 6. A kit for identifying benign and malignant thyroid nodules, the kit comprising reagents for detecting the mutation sites of genes from the group consisting of: GNAS gene: NM_016592:exon1:c.C205A; TSHR gene: NM_000369:exon10:c.A2252G; BRAF gene: NM_004333:exon15:c.T1799A。
  7. 7. The kit of claim 4, further comprising reagents for detecting mutation sites of the following genes: GNAS gene: NM_016592:exon1:c.C216T, and/or The kit also comprises detection reagents for the following gene mutation sites: TSHR gene: NM_000369:exon10:c.A2098G。
  8. 8. The kit of claim 4, further comprising a detection reagent for one or more gene mutation sites selected from the group consisting of: BRAF gene: NM_004333:exon11:c.G1338A、 NM_004333:exon15:c.A1801G; CHEK2 gene: NM_145862:exon10:c.C1024T; NRAS gene: NM_002524:exon3:c.C181A、NM_002524:exon3:c.A182G; AKT1 gene: NM_001014431:exon3:c.G49A; PPM1D gene: NM_003620:exon1:c.C262T; PTEN gene: NM_000314:exon5:c.C328T; RET gene: NM_020630:exon11:c.T1888C、NM_020630:exon16:c.T2753C; TP53 Gene: NM_001126115:exon3:c.C265T、NM_000546:exon8:c.G814T; And/or the kit further comprises a detection reagent for one or more fusion genes selected from the group consisting of: ETV6-NTRK3 fusion gene: ETV6{ENST00000396373}:r.1_737_NTRK3{ENST00000394480}:r.1719_19984; NCOA4-RET fusion gene: NCOA4{ENST00000452682}:r.1_1014_RET{ENST00000355710}:r.2369_5659; CCDC6-RET fusion gene: CCDC6{ENST00000263102}:r.1_535_RET{ENST00000355710}:r.2369_5659。
  9. 9. The kit of claim 4, wherein the detection reagent is: (A) Specific primers for gene detection; (B) A specific probe for gene detection; (C) Chip for gene detection, or (D) A specific antibody for detecting an amino acid mutation corresponding to a mutated gene.
  10. 10. A method for non-diagnostic in vitro detection of the presence or absence of a genetic mutation in a sample, comprising the steps of: (a) Amplifying the polynucleotides of the sample with specific primers to obtain amplified products, and (B) Detecting the presence or absence of a combination of the following gene mutations in the amplified product: GNAS gene: NM_016592:exon1:c.C205A; TSHR gene: NM_000369:exon10:c.A2252G; BRAF gene: NM_004333:exon15:c.T1799A。

Description

Gene polymorphism site related to thyroid cancer and application thereof The present application is a divisional application of Chinese invention patent application with the application date of 2017, 06 month and 06, the application number of CN 201710438578.9 and the invention name of ' gene somatic cell specific mutation site related to thyroid nodule ' and application thereof '. Technical Field The invention belongs to the field of biological medicine, and in particular relates to a gene somatic cell specific mutation site related to thyroid nodule and application thereof. Background Thyroid nodules are one of the most common thyroid diseases in the clinic, and the prevalence of thyroid nodules that palpation can find is about 4-7% in the adult population in the united states. Whereas with sensitive thyroid B examination, the prevalence of thyroid nodules is as high as 50% or more in the population over 65 years old. The research results of epidemiological investigation of thyroid diseases of 15,181 residents in ten cities of China, which were conducted by the society of endocrinology Teng Weiping professor of China in 2010, found that the prevalence of thyroid nodules in the population of China was as high as 18.6%, so that it was presumed that the patients of thyroid nodules in our country were as high as 2 hundred million people. Most thyroid nodules are benign and conservative treatment can be taken, but 5-10% of thyroid nodules are malignant and require early surgical treatment to obtain a good prognosis. Thus, a physician in a thyroid specialty department is faced with a great challenge in identifying benign and malignant thyroid nodules in a patient, and only then is the patient reasonably treated in a timely manner. If there are a large number of benign thyroid nodules that do not require surgery, the surgical treatment is inappropriately administered, and thus a large prevalence of people will create a huge medical insurance burden, whereas if there are no real malignant tumors identified from the large number of benign nodules, the treatment of these patients will be delayed, endangering the life and health of the patients. The means for identifying benign and malignant thyroid nodule in clinical use at present mainly comprise thyroid B ultrasonic, nuclide scanning and thyroid nodule Fine needle puncture pathological biopsy (Fine-needle Aspiration Biopsy, FNAB). Among them, the cytological biopsy of thyroid fine needle puncture is the gold standard of the present diagnosis of benign and malignant thyroid nodule. According to the guideline of the special conference of the thyroid fine needle puncture pathology in 2008 of the national cancer institute, the diagnosis of thyroid nodule puncture cytology is divided into four categories, namely 1, the diagnosis can not be performed due to insufficient number of thyroid cells, 2, benign nodule, 3, the diagnosis can not be performed by pathological cytology, and 4, malignant thyroid nodule. In recent years, with the wide application of the B-ultrasonic guidance for fine needle puncture, the proportion of patients who cannot be diagnosed due to the insufficient cell number obtained by puncture is obviously reduced from the previous 15% to below 7%. After a fine needle puncture has obtained enough thyroid follicular cells, most benign and malignant thyroid nodules can be correctly diagnosed by cytopathological diagnostic methods. However, even the currently internationally best laboratory for diagnosis of thyroid cytopathology has thyroid nodules with 20-40% of successful punctures that cannot be confirmed as benign or malignant, i.e., those with undiagnosed pathology. Therefore, when a patient performs a thyroid puncture pathological biopsy, the ratio of failure in puncture and failure in pathological judgment to make a correct diagnosis for the patient is as high as 30-50%, which is greatly affected by the technical level of thyroid pathological diagnosticians and puncture doctors at each center. Disclosure of Invention The invention aims to provide a pathogenic gene mutation site for thyroid cancer incidence and application thereof. In a first aspect of the invention there is provided the use of one or more gene mutation sites selected from the group (I) and/or detection reagents thereof for the preparation of a reagent or kit for identifying a benign malignancy of a thyroid nodule, said group (I) comprising the following gene mutation sites: GNAS gene: NM_001077490:exon1:c.T1019C; NRAS gene: NM_002524:exon3:c.T284C; TSHR gene: NM_000369:exon10:c.A2098G。 in another preferred embodiment, the group (I) further comprises the following gene mutation sites: CHEK2 gene: NM_145862:exon11:c.A1250G。 in another preferred embodiment, the group (I) further comprises the following gene mutation sites: PIK3CA gene: NM-006218 exon12 c.1818 bit lacks C. In another preferred embodiment, the group (I) further comprises the following gene mutation sites: GNAS gene: NM_0