Method of predicting reaction to sorafenib treatment using gene polymorphism

Patent metadata

Field	Value
Publication number	US-2017211147-A1
Application number	US-201515302872-A
Country	US
Kind code	A1
Filing date	Mar 23, 2015
Priority date	Apr 9, 2014
Publication date	Jul 27, 2017
Grant date	—

Abstract

The present invention relates to a method of predicting reaction to Sorafenib treatment using genetic polymorphism. More specifically, for the reaction to Sorafenib treatment according to the present invention, it is possible to predict the reaction of a test object to Sorafenib treatment by using an anticancer-target gene which is expressed in a biological sample of a liver cancer patient as a biomarker, whereby a proper drug is administered to a liver cancer patient and an optimal treatment effect is attained, so that inconvenience of a patient can be reduced, costs for treatment can be reduced, and an individually tailored chemotherapy can more effectively be implemented by administration of a patient-specific anticancer agent.

First claim

1 . A method of predicting the response to sorafenib treatment, comprising:
obtaining a sample from a subject, and detecting the absence or presence of an SLC15A2 genetic polymorphism.

2 . The method of claim 1 , wherein the SLC15A2 genetic polymorphism is a C-to-T variation at the 501 st nucleotide in an SLC15A2 gene (NCBI ACESSION NO: NM_021082; SEQ. ID. NO: 4).

3 . The method of claim 1 , wherein the subject is a liver cancer patient, and the sample is blood.

4 . The method of claim 1 , wherein the method comprises:
obtaining a sample from a subject, and determining if the 501 st nucleotide in an SLC15A2 gene (NCBI ACESSION NO: NM_021082; SEQ. ID. NO: 4) of the subject has a C/T or T/T genotype; and predicting the response of the subject with respect to sorafenib treatment based on the determination, wherein the presence of the C/T or T/T genotype is evaluated as superior in response to sorafenib treatment, compared to a subject with a C/C genotype.

5 . The method of claim 4 , wherein the determining of a genotype comprises amplifying the SLC15A2 gene using a set of primers set forth in SEQ. ID. NO: 1 and SEQ. ID. NO: 2, and detecting single-nucleotide polymorphisms (SNPs) present in the 501 st nucleotide in the SLC15A2 gene by sequencing.

6 . A marker composition for predicting the response to sorafenib treatment, comprising:
an agent for detecting the absence or presence of an SLC15A2 genetic polymorphism.

7 . The marker composition of claim 6 , wherein the SLC15A2 genetic polymorphism is a C-to-T variation at the 501 st nucleotide in an SLC15A2 gene (NCBI ACESSION NO: NM_021082; SEQ. ID. NO: 4).

8 . The marker composition of claim 6 , wherein the agent for detecting the absence or presence of the SLC15A2 genetic polymorphism comprises a set of primers set forth in SEQ. ID. NO: 1 and SEQ. ID. NO: 2.

9 . The marker composition of claim 6 , wherein, when the 501 st nucleotide in the SLC15A2 gene (NCBI ACESSION NO: NM_021082; SEQ. ID. NO: 4) has a C/T or T/T genotype, it is evaluated that a superior response to sorafenib treatment is exhibited, compared to a subject with a C/C genotype.

10 . A diagnosis kit for predicting the response to sorafenib treatment, comprising:
the marker composition of claim 6 .

11 . The diagnosis kit of claim 10 , which is an RT-PCR kit or a DNA chip kit.

12 . The diagnosis kit of claim 11 , wherein the DNA chip kit comprises primers or probes that are immobilized to a substrate, so as to detect a polymorphism at the 501 st nucleotide in an SLC15A2 gene (NCBI ACESSION NO: NM_021082; SEQ. ID. NO: 4), and may include a labeling means for detecting hybridization between the DNA chip and a sample.

13 . The diagnosis kit of claim 12 , wherein probes comprising a positive control hybridized with all nucleotide sequences in the sample and a negative control not hybridized with any nucleotide sequence are bound to a surface of the substrate.

Assignees

• Nat Cancer Ct

Inventors

• Pakr Joong-Won
• Lee Yeon Su
• Kim Bo Hyun

Classifications

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title