Cargando…

Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts

BACKGROUND: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction...

Descripción completa

Detalles Bibliográficos
Autores principales: Whiley, Phillip J, Pettigrew, Christopher A, Brewster, Brooke L, Walker, Logan C, Spurdle, Amanda B, Brown, Melissa A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897790/
https://www.ncbi.nlm.nih.gov/pubmed/20507642
http://dx.doi.org/10.1186/1471-2350-11-80
_version_ 1782183435415060480
author Whiley, Phillip J
Pettigrew, Christopher A
Brewster, Brooke L
Walker, Logan C
Spurdle, Amanda B
Brown, Melissa A
author_facet Whiley, Phillip J
Pettigrew, Christopher A
Brewster, Brooke L
Walker, Logan C
Spurdle, Amanda B
Brown, Melissa A
author_sort Whiley, Phillip J
collection PubMed
description BACKGROUND: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge. METHODS: This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches. RESULTS: Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing. CONCLUSIONS: These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.
format Text
id pubmed-2897790
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-28977902010-07-07 Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts Whiley, Phillip J Pettigrew, Christopher A Brewster, Brooke L Walker, Logan C Spurdle, Amanda B Brown, Melissa A BMC Med Genet Research Article BACKGROUND: Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge. METHODS: This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches. RESULTS: Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing. CONCLUSIONS: These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein. BioMed Central 2010-05-28 /pmc/articles/PMC2897790/ /pubmed/20507642 http://dx.doi.org/10.1186/1471-2350-11-80 Text en Copyright ©2010 Whiley et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Whiley, Phillip J
Pettigrew, Christopher A
Brewster, Brooke L
Walker, Logan C
Spurdle, Amanda B
Brown, Melissa A
Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
title Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
title_full Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
title_fullStr Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
title_full_unstemmed Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
title_short Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts
title_sort effect of brca2 sequence variants predicted to disrupt exonic splice enhancers on brca2 transcripts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897790/
https://www.ncbi.nlm.nih.gov/pubmed/20507642
http://dx.doi.org/10.1186/1471-2350-11-80
work_keys_str_mv AT whileyphillipj effectofbrca2sequencevariantspredictedtodisruptexonicspliceenhancersonbrca2transcripts
AT pettigrewchristophera effectofbrca2sequencevariantspredictedtodisruptexonicspliceenhancersonbrca2transcripts
AT brewsterbrookel effectofbrca2sequencevariantspredictedtodisruptexonicspliceenhancersonbrca2transcripts
AT walkerloganc effectofbrca2sequencevariantspredictedtodisruptexonicspliceenhancersonbrca2transcripts
AT spurdleamandab effectofbrca2sequencevariantspredictedtodisruptexonicspliceenhancersonbrca2transcripts
AT brownmelissaa effectofbrca2sequencevariantspredictedtodisruptexonicspliceenhancersonbrca2transcripts