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Fusion gene of CEP55 gene and RET gene

A fusion point and base technology, applied in the field of fusion genes, can solve the problem of not being sufficient, achieve high-efficiency cancer treatment, and achieve the effect of cancer treatment

Inactive Publication Date: 2015-05-13
NAT CANCER CENT +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] However, the current situation is that the elucidation of fusion genes in cancers including gastric cancer is not yet sufficient, and it is expected to greatly contribute to the development of new cancer treatment methods or cancer detection methods, and further, it can become a tool for predicting treatment with drugs. Identification of fusion genes, etc. as indicators of effectiveness

Method used

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  • Fusion gene of CEP55 gene and RET gene
  • Fusion gene of CEP55 gene and RET gene
  • Fusion gene of CEP55 gene and RET gene

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0152] [Identification of Novel Kinase Fusion Genes Using RNA Sequencing]

[0153] From the clinical samples of diffuse gastric cancer in 13 cases, on the basis of removing duplicate clones by PCR, 8.0×10 7 The above paired base sequence. Comparing these to the existing gene database, the results, such as figure 2 As shown, in one case, a fusion gene candidate encoding a CEP55 gene and a RET gene (a polynucleotide encoding a polypeptide fused to a CEP55 protein and a RET9 protein, a polynucleotide encoding a polypeptide fused to a CEP55 protein and a RET51 protein, hereinafter also referred to as referred to as "CEP55-RET fusion gene").

[0154] [Confirmation by RT-PCR and Sanger sequencing]

[0155] Next, verification of the fusion gene by RT-PCR and Sanger sequencing was performed using the same sample. As a result, by RT-PCR, case-specific amplification of the above-mentioned fusion gene was found, that is, expression of the above-mentioned fusion gene was found only i...

Embodiment 2

[0159] [Assessment of the function of the CEP55-RET fusion polypeptide and the effectiveness of RET tyrosine kinase inhibitors on cancer cells expressing the polypeptide]

[0160] It is considered that the above-mentioned gene fusion leads to the activation of the RET protein, and this activation also activates its downstream signals, resulting in the canceration of the cells. Therefore, it can be considered that RET tyrosine kinase inhibitors are effective in the treatment of patients with such activation. Therefore, for these observations, the CEP55-RET fusion gene was analyzed according to an appropriate conventional method as shown below.

[0161] First, the cDNA encoding the FLAG epitope tag (epitope tag) and the cDNA of the CEP55-RET fusion gene (polynucleotide encoding the fusion polypeptide of the CEP55 protein and the RET51 protein) obtained from the cancer tissue derived from the undifferentiated gastric cancer patient were combined. The 5' side was ligated in accor...

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Abstract

The purpose of the present invention is to identify a gene that can serve as a measure for the prognosis of the effectiveness of a drug-using therapy in cancer, and to provide a novel method for predicting the effectiveness of a drug-using therapy employing the gene as a target. An in-frame fusion transcript of CEP55 gene and RET gene is identified by the transcriptome sequencing of diffuse-type gastric cancer. It is found that this gene fusion induces the activation of RET protein and can transform a cell into a cancer cell. It is demonstrated that a RET tyrosine kinase inhibitor can inhibit the activation of RET protein and the transformation into a cancer cell both of which can be induced by the gene fusion. Thus, it is found that a therapy using a RET tyrosine kinase inhibitor is effective for a patient in which the gene fusion is detected.

Description

technical field [0001] The present invention relates to a fusion gene of a CEP55 gene and a RET gene, more specifically, a polynucleotide encoding a fusion polypeptide of a CEP55 protein or a part thereof and a RET protein or a part thereof, a polypeptide encoded by the polynucleotide, And a method for detecting the polynucleotide or the polypeptide. In addition, the present invention relates to a method for determining the effectiveness of cancer therapy using a RET tyrosine kinase inhibitor targeting the polynucleotide or the polypeptide. In addition, the present invention relates to a method for treating cancer using the determination of effectiveness. Furthermore, the present invention also relates to a drug used in these methods. Background technique [0002] Gastric cancer is the second most deadly cancer in the world, and it is one of the cancers with a large number of patients in East Asia. With the advancement of early diagnosis techniques mainly based on endosco...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/09A61K45/00A61P35/00A61P43/00C07K14/47C12Q1/68G01N33/53G01N33/574
CPCG01N33/574C12Q1/6886C12Q2600/106C07K14/4702C12N9/12C12Y207/10001C07K2319/00G01N33/57446G01N2800/52C07K14/71C07K14/82A61P35/00A61P43/00C07K16/32C12Q2600/158G01N33/5748
Inventor 柴田龙弘细田文惠
Owner NAT CANCER CENT
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