Portal de investigación
Investigating the effect of 28 BRCA1 and BRCA2 mutations on their related transcribed mRNA
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Quiles, F
- Menendez, M
- Tornero, E
- del Valle, J
- Teule, A
- Izquierdo, A
- Gomez, C
- Campos, O
- Santamaria, R
- Brunet, J
- Capella, G
- Feliubadalo, L
- Lazaro, C
Grupos
Abstract
Germline inactivating mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome (HBOCS). Genetic testing of these genes identifies a significant proportion of variants of uncertain significance (VUS). Elucidation of the clinical impact of these variants is an important challenge in genetic diagnostics and counseling. In this study, we assess the RNA effect of 28 BRCA1 and BRCA2 VUS identified in our set of HBOCS families with the aim of gaining insight into their clinical relevance. mRNA was extracted from VUS carriers and controls lymphocytes cultured for 5-6 days and treated with puromycin. RNA was reverse transcribed to perform transcriptional analysis for the study of splicing aberrations. In silico prediction tools were used to select those variants most likely to affect the RNA splicing process. Six out of the 28 variants analyzed showed an aberrant splicing pattern and could therefore be classified as probably pathogenic mutations. Reclassification of VUS improves the genetic counseling and clinical surveillance of carriers of these mutations and highlights the importance of RNA studies in routine diagnostic laboratories.
Datos de la publicación
- ISSN/ISSNe:
- 0167-6806, 1573-7217
- Tipo:
- Article
- Páginas:
- 253-260
- Factor de Impacto:
- 2,181 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
BREAST CANCER RESEARCH AND TREATMENT SPRINGER
Citas Recibidas en Web of Science: 6
Documentos
- No hay documentos
Filiaciones
Keywords
- BRCA1; BRCA2; VUS; Splicing; RNA
Proyectos asociados
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Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO
PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014
SISTEMA DE DETECCION DE BIOMARCADORES ONCOLOGICOS PARA TRATAMIENTO PERSONALIZADO DEL CANCER COLORRECTAL (ONCOMARKER).
Investigador Principal: SARAI PALANCA SUELA
RTC-2015-3625-1 . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD . 2015
Cita
Quiles F,Menendez M,Tornero E,del Valle J,Teule A,Palanca S,Izquierdo A,Gomez C,Campos O,Santamaria R,Brunet J,Capella G,Feliubadalo L,Lazaro C. Investigating the effect of 28 BRCA1 and BRCA2 mutations on their related transcribed mRNA. Breast Cancer Res Treat. 2016. 155. (2):p. 253-260. IF:3,626. (2).