[go: up one dir, main page]

WO2014084431A1 - Marqueur d'adn pour prédiction pronostique pour chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules non résécable - Google Patents

Marqueur d'adn pour prédiction pronostique pour chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules non résécable Download PDF

Info

Publication number
WO2014084431A1
WO2014084431A1 PCT/KR2012/010351 KR2012010351W WO2014084431A1 WO 2014084431 A1 WO2014084431 A1 WO 2014084431A1 KR 2012010351 W KR2012010351 W KR 2012010351W WO 2014084431 A1 WO2014084431 A1 WO 2014084431A1
Authority
WO
WIPO (PCT)
Prior art keywords
snp
small cell
platinum
patients
lung cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2012/010351
Other languages
English (en)
Korean (ko)
Inventor
이경원
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gyeongsang National University GNU
Original Assignee
Gyeongsang National University GNU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gyeongsang National University GNU filed Critical Gyeongsang National University GNU
Priority to PCT/KR2012/010351 priority Critical patent/WO2014084431A1/fr
Publication of WO2014084431A1 publication Critical patent/WO2014084431A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • the present invention relates to a DNA marker, and more particularly to a DNA marker for predicting the prognosis of the first platinum-based chemotherapy treatment of patients with non-resectable non-small cell lung cancer.
  • Excision repair cross-complementing group 2 also called xeroderma pigmentosum group D (XPD)
  • SNP single nucleotide polymorphism
  • SNPs have been identified on several exons of ERCC2, including codon 312 of exon 10 and codon 751 of exon 23.
  • the SNPs are known to cause amino acid mutations of Asp312Asn and Lys751Cln, respectively (Ott et al ., Ann. Surg. Oncol ., 18 (9): 2688-2698, 2011).
  • Correlation between SNP and platinum-based anticancer activity of the ERCC2 gene has been reported in patients with bronchial cancer, gastric cancer, colorectal cancer, bladder cancer and non-small cell lung cancer (Ott et al ., Ann. Surg. Oncol ., 18 (9)).
  • the present invention has been made to solve a number of problems including the above problems, and an object thereof is to provide a DNA marker that can predict the prognosis of patients when applying primary platinum-based chemotherapy to patients with non-resectable non-small cell cancer .
  • these problems are exemplary, and the scope of the present invention is not limited thereby.
  • a DNA marker for predicting the prognosis of primary platinum-based chemotherapy in patients with non-small cell cancer comprising rs50872 (G> A) SNP.
  • a DNA marker for predicting prognosis of primary platinum-based and taxane combination therapy in patients with non-small cell cancer comprising rs238405 (T> A) SNP.
  • a DNA marker for prognostic prediction of primary platinum-based and gemcitabine combination therapy in a non-small cell cancer patient comprising rs238416 (T> C) SNP is provided.
  • DNA analysis methods for prognostic prediction of -based chemotherapy are provided.
  • DNA analysis methods for prognostic prediction of primary platinum-based and taxane combination therapy are provided.
  • DNA analysis methods for prognostic prediction of primary platinum-based and gemcitabine combination therapy are provided.
  • the prognosis according to primary platinum-based chemotherapy and the prognosis according to primary-platinum-based and taxane or gemcitabine combination in the population of non-resectable non-small cell lung cancer are more accurately predicted.
  • the treatment and management of diseases in these populations can be carried out more efficiently.
  • FIG. 1 shows Kaplan-Meier curves for overall survival (A) and progression free survival (B) of non-small cell lung cancer patients treated with primary platinum-based chemotherapy according to genotype of rs50872 SNP. The graph shown.
  • FIG. 3 shows Kaplan-Meier curves for overall survival (A) and progression-free survival (B) of non-small cell lung cancer patients treated with primary platinum-based and gemcitabine combination therapy according to genotype of rs238416 SNP. curve).
  • a DNA marker for predicting the prognosis of primary platinum-based chemotherapy in patients with non-small cell cancer comprising rs50872 (G> A) SNP.
  • rs50872 (G> A) SNP may have a nucleic acid sequence of SEQ ID NO: 1, the 26th base in the nucleic acid sequence may be G.
  • a DNA marker for predicting prognosis of primary platinum-based and taxane combination therapy in patients with non-small cell cancer comprising rs238405 (T> A) SNP.
  • rs238405 (T> A) SNP may have a nucleic acid sequence of SEQ ID NO: 2, the 27th base in the nucleic acid sequence may be A.
  • a DNA marker for prognostic prediction of primary platinum-based and gemcitabine combination therapy in a non-small cell cancer patient comprising rs238416 (T> C) SNP is provided.
  • the rs238416 (T> C) SNP may have a nucleic acid sequence of SEQ ID NO: 3, and the 27th base in the nucleic acid sequence may be C.
  • DNA analysis methods for prognostic prediction of -based chemotherapy are provided.
  • DNA analysis methods for prognostic prediction of primary platinum-based and taxane combination therapy are provided.
  • DNA analysis methods for prognostic prediction of primary platinum-based and gemcitabine combination therapy are provided.
  • Pathologically determined patients with non-small cell lung cancer treated with platinum-based anticancer drugs (cisplatin 20-25 mg / m 2 at weekly intervals for patients with stage IIIa or IIIb who have undergone concurrent chemoradiotherapy) Or carboplatin AUC 2; cisplatin 40 mg / m 2 or biweekly cisplatin 60-75 mg / m 2 or carboplatin AUC 4-5 every other week on days 1 and 15), Gemcitabine 1000 mg / m 2 or taxane (docetaxel 20-25 mg / m 2 at weekly intervals of days 1 and 8; days 1 and 8; Docetaxel 40 mg / m 2 at biweekly intervals of 15 days; Docetaxel 60-75 mg / m 2 at 3-week intervals of day 1; Paclitaxel (at weekly intervals of days 1, 8 and 15) paclitaxel) 60 mg / m 2 ; or paclitaxel 175 mg / m 2 ) at 3 week intervals
  • SNPs single nucleotide polymorphisms
  • the additional SNP was selected from the public International HapMap Project Phase II database (//www.ncbi.nih.gov/; available at //www.hapmap.org/, The International HapMap Project.Nature 426 (6968): 789-796, 2003).
  • algorithm-Tagger-pairwise method only htSNPs with a frequency of minor portions greater than 10% were considered, and the threshold of pairwise linkage disequilibrium was set to a squared correlation coefficient (R 2 )> 0.8.
  • htSNP was chosen from the Han Chinese and Japanese groups. We chose 8 htSNPs in ERCC2 (Table 2). The allele frequencies of these eight SNPs in the control group were at Hardy-Weinberg equilibrium.
  • Genotyping of DNA samples was performed as previously reported using a MALDI mass spectrometer (matrix-assisted laser desorption / ionization of time of flight, Sequenome, USA) (Phillips et al ., Nat. Genet ., 33 (3): 382-387, 2003).
  • Polymerase chain reaction (PCR) analysis and related expansion reactions were designed using SpectroDESIGNER (Sequenom, USA), and primers for this were customized from Bioneer (South Korea).
  • All amplification reactions consisted of 2.5 ng of genomic DNA, 1 pmol of each primer, 0.2 mmol / L of trioxydiphosphate, 2.5 mmol / L of MgCl 2 , and HotStart DNA polymerase (Bioneer, South Korea) 0.2 under the same conditions with a total volume of 5 ⁇ l. It was performed using U. The reaction was heated at 95 ° C. for 15 minutes, followed by 45 cycles of amplification (20 seconds at 94 ° C., 30 seconds at 60 ° C. and 30 seconds at 72 ° C.), and finally extended at 72 ° C. for 7 minutes.
  • Expansion reactions are performed using the allele-specific extension primer prior to cleaning using SpectroCLEANER (Sequenom, USA) on a MULTIMEK 96 automated 96-channel robot (Beckman Coulter, USA). 5 pmol of the primer) and a mass volume of 9 ⁇ l using a Mass EXTEND Reagents Kit. Clean primer extension products were loaded onto 384-well chips using a nanoliter pipetting system (SpectroCHIP, SpectroJet, Sequenom, USA) and analyzed by MassARRAY mass spectrometer (Bruker Daltonik, Germany) . Calculated peaks were identified using SpectroTYPER RT 2.0 (Sequenom, USA).
  • ERCC2 polymorphisms were analyzed according to haplotypes. The analysis determined the association between polymorphisms, demographics, pretreatment characteristics, and outcome data (eg response to treatment, survival, and side effects). Pearson's chi-square tests were used to determine the relationship between the variables in each category and the ERCC2 genotype / haplotype. Survival was calculated from the time of pathological confirmation until the last review until the death from any cause.
  • the Hazard ratio (HR) with 95% confidence interval (CIS) is the Cox proportional to haplotype, histological subgroup, performance status, and stage of cancer. Calculations were made using Cox proportional hazards regression. Differences in survival rates between haplotypes and additional prognostic groups were compared using the Kaplan-Meier method and log-rank tests. All statistical tests were two-sided and performed with SPSS version 18.0 (SPSS, USA).
  • the median survival duration (MSD) of the rs50872 G / G, A / G, and A / A genotypes was 35.75 months (95% confidence interval 24.41-47.09) and 36.07 months (HR 1.02 [0.54-1.92], 95% confidence interval 25.20-46.94) and 16.75 months (HR 3.49 [1.41-8.62], 95% confidence interval 5.73-27.77) (A in FIG. 1).
  • the progression free median survival (PFS) of the rs50872 G / G, A / G, and A / A genotypes was 13 months (95% confidence interval 0-31.80), 12.6 months, and 4.21 month (95% confidence interval), respectively. 1.82-6.61) months (FIG. 1B).
  • OS for grade 2 infections and poor survival grade 0-3 infections 35.75 months [28.15-43.35 CI 95%]; OS for grade 3-4 infection: 12.86 months [95% CI 8.99-16.72, HR 3.57])
  • Significant correlations were based on log-rank test. (P ⁇ 0.0001 Table 3). This means that in the rs50872 SNP, if either allele has a major allele G, the prognosis is good.
  • PFS progression free median survival
  • the progression free median survival (PSF) of the rs238405 T / T and T / A genotypes was 6.18 months (95% confidence interval 5.31-7.05) and 14.18 months, respectively.
  • PFS for the A / A genotype was not calculated (FIG. 2B).
  • the results indicate that in rs50872 SNP, the prognosis is good when either allele has a major allele, and the prognosis is the best when it has the A / A genotype.
  • the progression free median survival (PFS) of the rs238416 C / T genotype was 6.21 months (95% confidence interval 4.45-7.98) and no PFS of the rs238416 C / C and T / T genotypes was calculated (FIG. 3B). .
  • the rs238416 had a better prognosis for the C / C and T / T homozygous genotypes, and for the heterogenous C / T, the prognosis was poor.
  • rs50872 SNP is useful as a marker for predicting the prognosis of primary platinum-based chemotherapy treatment in patients with non-small cell lung cancer
  • rs238405 SNP is a combination therapy of primary platinum-based and taxane-based anticancer agents in non-small cell lung cancer patients.
  • Useful as a marker for predicting prognosis in use it can be seen that rs238416 SNP can be useful as a marker for predicting prognosis when using primary platinum-based and gemcitabine combination therapy in patients with non-small cell lung cancer.
  • the patient according to the first platinum-based chemotherapy Accurately predicting the prognosis can help to establish the correct treatment and management of the patient.
  • SEQ ID NO: 1 is a nucleic acid sequence showing rs50872 SNP of ERCC2.
  • SEQ ID NO: 2 is a nucleic acid sequence showing rs238405 SNP of ERCC2.
  • SEQ ID NO: 3 is a nucleic acid sequence showing rs238416 SNP of ERCC2.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne la fourniture d'un marqueur d'ADN pour une prédiction pronostique pour une chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules, comprenant un polymorphisme mononucléotidique rs50872 (G>A) pour une prédiction pronostique précise pour une chimiothérapie à base de platine de première intention pour des patients atteints d'un cancer du poumon non à petites cellules.
PCT/KR2012/010351 2012-11-30 2012-11-30 Marqueur d'adn pour prédiction pronostique pour chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules non résécable Ceased WO2014084431A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/KR2012/010351 WO2014084431A1 (fr) 2012-11-30 2012-11-30 Marqueur d'adn pour prédiction pronostique pour chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules non résécable

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2012/010351 WO2014084431A1 (fr) 2012-11-30 2012-11-30 Marqueur d'adn pour prédiction pronostique pour chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules non résécable

Publications (1)

Publication Number Publication Date
WO2014084431A1 true WO2014084431A1 (fr) 2014-06-05

Family

ID=50828048

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2012/010351 Ceased WO2014084431A1 (fr) 2012-11-30 2012-11-30 Marqueur d'adn pour prédiction pronostique pour chimiothérapie à base de platine de première intention pour patients atteints d'un cancer du poumon non à petites cellules non résécable

Country Status (1)

Country Link
WO (1) WO2014084431A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100216826A1 (en) * 2006-03-03 2010-08-26 University Of Southern California Polymorphisms in Voltage-Gated Sodium Channel Alpha 1-Subunit as Markers for Therapy Selection
WO2012028679A2 (fr) * 2010-09-01 2012-03-08 Institut Gustave Roussy Biomarqueurs pronostics et/ou prédictifs et leurs applications biologiques

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100216826A1 (en) * 2006-03-03 2010-08-26 University Of Southern California Polymorphisms in Voltage-Gated Sodium Channel Alpha 1-Subunit as Markers for Therapy Selection
WO2012028679A2 (fr) * 2010-09-01 2012-03-08 Institut Gustave Roussy Biomarqueurs pronostics et/ou prédictifs et leurs applications biologiques

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HAN, WONSHIK ET AL.: "SNP-SNP interactions between DNA repair genes were associated with breast cancer risk in a Korean population", CANCER, vol. 118, no. 3, 12 July 2011 (2011-07-12), pages 594 - 602 *
KIM, SEOK-HYUN ET AL.: "Clinical significance ofERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy", LUNG CANCER, vol. 77, no. 3, 18 May 2012 (2012-05-18), pages 578 - 584 *
MA, WEN-JING ET AL.: "DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China", WORLD J. GASTROENTEROL., vol. 16, no. 5, 7 February 2010 (2010-02-07), pages 641 - 647 *

Similar Documents

Publication Publication Date Title
Wiklund et al. Genetic analysis of the RNASEL gene in hereditary, familial, and sporadic prostate cancer
Savage et al. Analysis of genes critical for growth regulation identifies Insulin-like Growth Factor 2 Receptor variations with possible functional significance as risk factors for osteosarcoma
Dai et al. The associations of single nucleotide polymorphisms in miR196a2, miR-499, and miR-608 with breast cancer susceptibility: a STROBE-compliant observational study
NZ581858A (en) Genetic variants on chr 5p12 and 10q26 as markers for use in breast cancer risk assessment, diagnosis, prognosis and treatment
Palli et al. GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population
US11421280B2 (en) Methods and composition for the prediction of the activity of enzastaurin
Ramsey et al. Cross‐species analysis of the canine and human bladder cancer transcriptome and exome
Lech‐Maranda et al. Polymorphisms of TNF and IL‐10 genes and clinical outcome of patients with chronic lymphocytic leukemia
Elematore et al. Association of genetic variants at TOX3, 2q35 and 8q24 with the risk of familial and early-onset breast cancer in a South-American population
Cipollini et al. TPO genetic variants and risk of differentiated thyroid carcinoma in two European populations
CN101535500B (zh) 乳腺癌标志物
Wrage et al. Identification of HERC 5 and its potential role in NSCLC progression
CA2656199A1 (fr) Modeles genetiques utilises pour la stratification des risques de cancer
Yarden et al. MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish–Ashkenazi descent
Gomes et al. Haplotypic characterization of BRCA1 c. 5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer
Diergaarde et al. Pooling-based genome-wide association study implicates gamma-glutamyltransferase 1 (GGT1) gene in pancreatic carcinogenesis
Cortes et al. Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes
Lindström et al. Comprehensive genetic evaluation of common E-cadherin sequence variants and prostate cancer risk: strong confirmation of functional promoter SNP
Yu et al. Genetic variants in GSTM3 gene within GSTM4-GSTM2-GSTM1-GSTM5-GSTM3 cluster influence breast cancer susceptibility depending on GSTM1
Farahbakhsh et al. TGF-β1 polymorphisms-509 C> T and+ 915 G> C and risk of pancreatic cancer
WO2015111852A1 (fr) Composition permettant de prédire le risque de leucopénie induite par une thiopurine, contenant un marqueur de polymorphisme mononucléotidique au sein du gène nudt15
Chen et al. Influence of TS and ABCB1 gene polymorphisms on survival outcomes of 5‑FU-based chemotherapy in a Chinese population of advanced gastric cancer patients
Takahashi et al. Japanese genome‐wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14
Wex et al. Interleukin 1 beta (IL1B) gene polymorphisms are not associated with gastric carcinogenesis in Germany
Hwang et al. Polymorphisms of interferon‐γ and interferon‐γ receptor 1 genes and pulmonary tuberculosis in Koreans

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12889048

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12889048

Country of ref document: EP

Kind code of ref document: A1