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Colocalised genetic associations reveal alternative splicing variants as candid...
Duarte, André; Carrasqueiro, Beatriz; Vieira de Sousa, Cármen Sofia; Gonçalves de Gouveia Maia Xavier, Joana; Maia, Ana-TeresaSimple Summary Hundreds of common genetic variants have been linked to breast cancer, but their exact mechanisms of action remain unclear. Understanding these mechanisms could lead to better prevention strategies and improved survival rates. Our study focused on how these variants influence splicing-a process by which a gene's coding elements are rearranged to produce different proteins. By analysing data from ...
Identification of candidate causal variants and target genes at 41 breast cance...
Gonçalves de Gouveia Maia Xavier, Joana; Magno, Ramiro; Russell, Roslin; Almeida, Bernardo P. de; Jacinta-Fernandes, Ana; Duarte, AndréUnderstanding breast cancer genetic risk relies on identifying causal variants and candidate target genes in risk loci identified by genome-wide association studies (GWAS), which remains challenging. Since most loci fall in active gene regulatory regions, we developed a novel approach facilitated by pinpointing the variants with greater regulatory potential in the disease’s tissue of origin. Through genome-wide...
Germline allelic expression of genes at 17q22 locus associates with risk of bre...
Esteves, Filipa; M Xavier, Joana; Ford, Anthony M.; Rocha, Cátia; Pharoah, Paul D. P.; Caldas, Carlos; Chin, Suet-Feung; Maia, Ana-TeresaIntroduction: Translation of genome-wide association study (GWAS) findings into preventive approaches is challenged by the identification of the causal risk variants and the understanding of the biological mechanisms by which they act. We present using allelic expression (AE) ratios to perform quantitative caseecontrol analysis as a novel approach to identify risk associations, causal regulatory variants, and t...
Quincunx: an R package to query, download and wrangle PGS catalog data
Magno, Ramiro; Duarte, Isabel; Maia, Ana-TeresaFor two decades, GWAS identified individual variants associated with risk for complex diseases. These associations can be combined into polygenic scores (PGS) aiming at quantifying an individual’s risk to disease, inform on prognosis and even treatment response (Lambert et al., 2019). Broadly, PGS use summary statistics produced by GWAS to calculate a weighted sum of trait-associated alleles carried by each ind...
THOR is a targetable epigenetic biomarker with clinical implications in breast ...
Apolónio, Joana; Dias, João S.; Fernandes, Mónica T.; Komosa, Martin; Lipman, Tatiana; Zhang, Cindy H.; Leão, Ricardo; Lee, Donghyun; Nunes, Nuno M.Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demon‑ strate the urgent need of novel and more efective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this proces...
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer a...
Correia, Lizelle; Magno, Ramiro; Xavier, JM; Almeida, Bernardo; Duarte, Isabel; Esteves, Filipa; Ghezzo, Marinella; Eldridge, Matthew; Sun, ChongPIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. W...
Allele-specific miRNA-binding analysis identifies candidate target genes for br...
Jacinta-Fernandes, Ana; Xavier, Joana M.; Magno, Ramiro; Lage, Joel; Maia, Ana-TeresaMost breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to ...
Gwasrapidd: an R package to query, download and wrangle GWAS catalog data
Magno, Ramiro; Maia, Ana-TeresaThe National Human Genome Research Institute Catalog of Published Genome-Wide Association Studies (GWAS) Catalog has collected, curated and made available data from over 7100 studies. The recently developed GWAS Catalog representational state transfer (REST) application programming interface (API) is the only method allowing programmatic access to this resource.
Epigenetic therapy in urologic cancers: an update on clinical trials
Faleiro, Inês; Leão, Ricardo; Binnie, Alexandra; de Mello, Ramon Andrade; Maia, Ana-Teresa; Castelo Branco, PedroEpigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clini...
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRC...
Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data fro...