SLC46A1 haplotype with predicted functional impact has prognostic value in breast carcinoma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F21%3A00013409" target="_blank" >RIV/75010330:_____/21:00013409 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023698:_____/21:N0000014 RIV/00216208:11140/21:10418534 RIV/00064203:_____/21:10418534 RIV/00216208:11130/21:10418534 RIV/70883521:28150/21:63527470

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s40291-020-00506-2" target="_blank" >https://link.springer.com/article/10.1007/s40291-020-00506-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s40291-020-00506-2" target="_blank" >10.1007/s40291-020-00506-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

SLC46A1 haplotype with predicted functional impact has prognostic value in breast carcinoma

Popis výsledku v původním jazyce

Background and Objective Membrane solute carrier transporters play an important role in the transport of a wide spectrum of substrates including anticancer drugs and cancer-related physiological substrates. This study aimed to assess the prognostic relevance of gene expression and genetic variability of selected solute carrier transporters in breast cancer. Methods Gene expression was determined by quantitative real-time polymerase chain reaction. All SLC46A1 and SLCO1A2 exons and surrounding non-coding sequences in DNA extracted from the blood of patients with breast cancer (exploratory phase) were analyzed by next-generation sequencing technology. Common variants (minor allele frequency >= 5%) with in silico-predicted functional relevance were further analyzed in a large cohort of patients with breast cancer (n = 815) and their prognostic and predictive potential was estimated (validation phase). Results A gene expression and bioinformatics analysis suggested SLC46A1 and SLCO1A2 to play a putative role in the prognosis of patients with breast cancer. In total, 135 genetic variants (20 novel) were identified in both genes in the exploratory phase. Of these variants, 130 were non-coding, three missense, and two synonymous. One common variant in SLCO1A2 and four variants in SLC46A1 were predicted to be pathogenic by in silico programs and subsequently validated. A SLC46A1 haplotype block composed of rs2239911-rs2239910-rs8079943 was significantly associated with ERBB2/HER2 status and disease-free survival of hormonally treated patients. Conclusions This study revealed the prognostic value of a SLC46A1 haplotype block for breast cancer that should be further studied.

Název v anglickém jazyce

SLC46A1 haplotype with predicted functional impact has prognostic value in breast carcinoma

Popis výsledku anglicky

Background and Objective Membrane solute carrier transporters play an important role in the transport of a wide spectrum of substrates including anticancer drugs and cancer-related physiological substrates. This study aimed to assess the prognostic relevance of gene expression and genetic variability of selected solute carrier transporters in breast cancer. Methods Gene expression was determined by quantitative real-time polymerase chain reaction. All SLC46A1 and SLCO1A2 exons and surrounding non-coding sequences in DNA extracted from the blood of patients with breast cancer (exploratory phase) were analyzed by next-generation sequencing technology. Common variants (minor allele frequency >= 5%) with in silico-predicted functional relevance were further analyzed in a large cohort of patients with breast cancer (n = 815) and their prognostic and predictive potential was estimated (validation phase). Results A gene expression and bioinformatics analysis suggested SLC46A1 and SLCO1A2 to play a putative role in the prognosis of patients with breast cancer. In total, 135 genetic variants (20 novel) were identified in both genes in the exploratory phase. Of these variants, 130 were non-coding, three missense, and two synonymous. One common variant in SLCO1A2 and four variants in SLC46A1 were predicted to be pathogenic by in silico programs and subsequently validated. A SLC46A1 haplotype block composed of rs2239911-rs2239910-rs8079943 was significantly associated with ERBB2/HER2 status and disease-free survival of hormonally treated patients. Conclusions This study revealed the prognostic value of a SLC46A1 haplotype block for breast cancer that should be further studied.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Molecular Diagnosis & Therapy

ISSN

1177-1062

e-ISSN

1179-2000

Svazek periodika

25

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NZ - Nový Zéland

Počet stran výsledku

12

Strana od-do

99-110

Kód UT WoS článku

000604226000001

EID výsledku v databázi Scopus

2-s2.0-85098518339