Use of Germline Genetic Variability for Prediction of Chemoresistance and Prognosis of Breast Cancer Patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F70883521%3A28150%2F18%3A63520841" target="_blank" >RIV/70883521:28150/18:63520841 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/18:43917437 RIV/00216208:11130/18:10383706 RIV/61989592:15110/18:73590334 RIV/00064203:_____/18:10383706 RIV/00023698:_____/18:N0000018

Výsledek na webu

<a href="http://dx.doi.org/10.3390/cancers10120511" target="_blank" >http://dx.doi.org/10.3390/cancers10120511</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers10120511" target="_blank" >10.3390/cancers10120511</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Use of Germline Genetic Variability for Prediction of Chemoresistance and Prognosis of Breast Cancer Patients

Popis výsledku v původním jazyce

The aim of our study was to set up a panel for targeted sequencing of chemoresistance genes and the main transcription factors driving their expression and to evaluate their predictive and prognostic value in breast cancer patients. Coding and regulatory regions of 509 genes, selected from PharmGKB and Phenopedia, were sequenced using massive parallel sequencing in blood DNA from 105 breast cancer patients in the testing phase. In total, 18,245 variants were identified of which 2565 were novel variants (without rs number in dbSNP build 150) in the testing phase. Variants with major allele frequency over 0.05 were further prioritized for validation phase based on a newly developed decision tree. Using emerging in silico tools and pharmacogenomic databases for functional predictions and associations with response to cytotoxic therapy or disease-free survival of patients, 55 putative variants were identified and used for validation in 805 patients with clinical follow up using KASP (TM) technology. In conclusion, associations of rs2227291, rs2293194, and rs4376673 (located in ATP7A, KCNAB1, and DFFB genes, respectively) with response to neoadjuvant cytotoxic therapy and rs1801160 in DPYD with disease-free survival of patients treated with cytotoxic drugs were validated and should be further functionally characterized.

Název v anglickém jazyce

Use of Germline Genetic Variability for Prediction of Chemoresistance and Prognosis of Breast Cancer Patients

Popis výsledku anglicky

The aim of our study was to set up a panel for targeted sequencing of chemoresistance genes and the main transcription factors driving their expression and to evaluate their predictive and prognostic value in breast cancer patients. Coding and regulatory regions of 509 genes, selected from PharmGKB and Phenopedia, were sequenced using massive parallel sequencing in blood DNA from 105 breast cancer patients in the testing phase. In total, 18,245 variants were identified of which 2565 were novel variants (without rs number in dbSNP build 150) in the testing phase. Variants with major allele frequency over 0.05 were further prioritized for validation phase based on a newly developed decision tree. Using emerging in silico tools and pharmacogenomic databases for functional predictions and associations with response to cytotoxic therapy or disease-free survival of patients, 55 putative variants were identified and used for validation in 805 patients with clinical follow up using KASP (TM) technology. In conclusion, associations of rs2227291, rs2293194, and rs4376673 (located in ATP7A, KCNAB1, and DFFB genes, respectively) with response to neoadjuvant cytotoxic therapy and rs1801160 in DPYD with disease-free survival of patients treated with cytotoxic drugs were validated and should be further functionally characterized.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/NV15-25618A" target="_blank" >NV15-25618A: Validace biomarkerů chemosensitivity karcinomu prsu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancers

ISSN

2072-6694

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

26

Strana od-do

2-26

Kód UT WoS článku

000455199200049

EID výsledku v databázi Scopus

2-s2.0-85058463495