A novel splicing mutation in the SLC9A3R1 gene in tumors from ovarian cancer patients

Authors
Kreimann, Erica Lorena; Ratajska, Magdalena; Kuzniacka, Alina; Demacopulo, Brenda; Stukan, Maciej; Limon, Janusz
Publication Year
2015
Language
English
Format
article
Status
Published version
Description
The aim of the present study was to investigate novel molecular markers that could improve the diagnosis of ovarian cancer patients or be of predictive value. The sequence of the sodium‑hydrogen antiporter 3 regulator 1 (SLC9A3R1) gene that codes for the PDZ2 motif of the Na+/H+ exchanger regulatory factor 1 (NHERF1) protein was analyzed. Changes in migration and cell transformation, and alterations of growth factor signaling pathways have been described in cells lacking endogenous NHERF1 or expressing an isoform lacking the function of the PDZ2 domain. Exons 2 and 3, together with flanking intronic sequences of the SLC9A3R1 gene, were amplified and bi‑directionally sequenced in 31 primary tumor samples from epithelial ovarian cancer patients. In total, 3 different previously undescribed mutations were detected in 8 out of 31 serous adenocarcinoma tumor samples (25.8%). Bioinformatics analysis predicted a significant effect in the splicing process as a result of the mutations that could disrupt the NHERF1 PDZ2 domain. Point mutations in consensus splicing recognition are a major cause of the splicing defects that are found in several diseases, including cancer. It has previously been shown that a lack of exon 2 and disruption of the PDZ2 domain contribute to cell transformation and leads to modifications in the physiological regulation of the confor­mational state of NHERF1. Further studies in bigger groups of ovarian cancer patients will determine the importance of this mutation in disease progression and patient survival.
Fil: Kreimann, Erica Lorena. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ratajska, Magdalena. Medical University of Gdansk; Polonia
Fil: Kuzniacka, Alina. Medical University of Gdansk; Polonia
Fil: Demacopulo, Brenda. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Stukan, Maciej. Gdynia Oncology Centre; Polonia
Fil: Limon, Janusz. Medical University of Gdansk; Polonia
Subject
MUTATION
OVARIAN CANCER
PDZ2
SLC9A3R1 GENE
SPLICING
Otras Medicina Básica
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Oncología
Medicina Clínica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/70697