RT info:eu-repo/semantics/doctoralThesis
T1 Alteración de los patrones de splicing en genes de susceptibilidad a cáncer de mama: análisis funcional mediante minigenes híbridos.
A1 Sanoguera Miralles, Lara
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Mamas Cáncer
K1 Breast/ovarian cancer
K1 Cáncer de mama/ovario
K1 Aberrant splicing
K1 Splicing aberrante
K1 Hybrid minigenes
K1 Minigenes híbridos
K1 3207.13 Oncología
AB 5-10% of all breast cancers are hereditary and, therefore, attributable to deleterious germline mutations in predisposition genes. Recently, two large case/control studies have revealed that 8 genes are significantly associated with breast cancer: BRCA1, BRCA2, PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. Screening of these genes using high-throughput sequencing has allowed the detection of thousands of variants, many of them classified as variants of unknown significance (VUS). Interestingly, splicing dysregulation is a prevalent etiopathogenic mechanism in breast cancer susceptibility genes. In this context, functional splicing assays of potentially spliceogenic variants reported in breast cancer susceptibility genes will allow the reclassification of a large fraction of VUS. The aim of this PhD thesis is to functionally and clinically classify splice site variants identified in the breast cancer predisposition genes CHEK2 and RAD51C, as well as to characterize the regulatory mechanisms involved in the inclusion of exons subject to alternative splicing, such as exons 8 and 10 of CHEK2, and special exons, such as BARD1 exon 4 (macroexon) and BRIP1 exon 1 (GC donor).
YR 2024
FD 2024
LK https://uvadoc.uva.es/handle/10324/66867
UL https://uvadoc.uva.es/handle/10324/66867
LA spa
NO Escuela de Doctorado
DS UVaDOC
RD 07-ago-2024