A5008283560- RNA Research and Splicing
- BRCA gene mutations in cancer
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Congenital Diaphragmatic Hernia Studies
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Genomics and Rare Diseases
- Neuroendocrine Tumor Research Advances
- Congenital Heart Disease Studies
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Ovarian cancer diagnosis and treatment
- Congenital heart defects research
- Thyroid Cancer Diagnosis and Treatment
- interferon and immune responses
- Tracheal and airway disorders
- Nutrition, Genetics, and Disease
- Metastasis and carcinoma case studies
McGill University
2014-2024
McGill Genome Centre
2020-2023
McGill University and Génome Québec Innovation Centre
2015-2019
Centre For Human Genetics
2018
Université de Sherbrooke
2005-2013
Bcl-x is a member of the Bcl-2 family proteins that are key regulators apoptosis. The pre-mRNA alternatively spliced to yield Bcl-xS and Bcl-xL, two isoforms have been associated, respectively, with promotion prevention We investigated some elements factors involved in production these splice variants. Deletion mutagenesis using human minigene identifies regions exon 2 modulate 5′-splice site selection HeLa cells. One region (B3) located upstream Bcl-xL enforces cells splicing extracts....
Localization of sentinel lymph nodes can be challenging if they are in difficult anatomic locations or near high radiotracer activity. The purpose this study was to assess the value intraoperative real-time imaging using a portable γ-camera conjunction with conventional γ-counting probe when it is localize node. <b>Methods:</b> After <sup>99m</sup>Tc-nanocolloid injection, patients various malignancies underwent presurgical lymphoscintigraphy followed by surgery (usually next day). We...
Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations hereditary syndromes. A previous whole-exome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 two children with overgrowth and developmental delay well more typical phenotypes germline mutation. However, very-low-frequency difficult to detect, thus, causal can go unnoticed. Highly sensitive, cost-effective approaches are needed molecularly...
Therapies targeting epidermal growth factor receptor (EGFR) have variable and unpredictable responses in breast cancer. Screening triple-negative cancer (TNBC) patient-derived xenografts (PDXs), we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated was significantly...
Abstract Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic elements have been associated with regulating levels core components spliceosome and alternative splicing downstream genes. Here we identify mutations one such element, exon SNRPB as cause cerebro–costo–mandibular syndrome. This contains premature termination codon that triggers nonsense-mediated mRNA decay when included transcript. These increased...
Alternative splicing is known to increase the complexity of mammalian transcriptomes since nearly all genes express multiple pre-mRNA isoforms. However, our knowledge extent and function alternative in early embryonic development based mainly on a few isolated examples. High throughput technologies now allow us study genome-wide during mouse development. A analysis isoform expression day 8.5, 9.5 11.5 embryos placenta was carried out using splicing-sensitive exon microarray. We show that...
The Bcl-x pre-mRNA is alternatively spliced to produce the anti-apoptotic Bcl-x(L) and pro-apoptotic Bcl-x(S) isoforms. By performing deletion mutagenesis on a human minigene, we have identified novel exonic element that controls use of 5' splice site Bcl-x(S). proximal portion this acts as repressor located downstream an enhancer. Further mutational analysis provided detailed topological map regulatory activities revealing sharp transition between enhancer sequences. Portions can function...
The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary and (HBOC). All variants were classified using information from population disease specific databases, silico prediction tools American College Medical Genetics Genomics (ACMG) criteria. Loss heterozygosity (LOH) tumor samples segregation analyses...
Alternative 5 ′ splice site selection allows Bcl-x to produce two isoforms with opposite effects on apoptosis. The pro-apoptotic Bcl-xS variant is up-regulated by ceramide and down-regulated protein kinase C through specific cis-acting exonic elements, one of which bound SAP155. Splicing the also enforced heterogeneous nuclear ribonucleoprotein (hnRNP) F/H proteins Sam68 in cooperation hnRNP A1. Here, we have characterized exon elements that influence splicing anti-apoptotic Bcl-xL isoform....
The alternative splicing of Bcl-x generates the proapoptotic Bcl-x(S) protein and antiapoptotic isoform Bcl-x(L). is coupled to signal transduction, since ceramide, hormones, growth factors alter ratio isoforms in different cell lines. Here we report that kinase C (PKC) inhibitor apoptotic inducer staurosporine switches production towards x(S) mRNA 293 cells. increase elicited by likely involves signaling events affect decisions, because it requires active transcription no new synthesis...
Abstract We report changes in the genomic landscape development of head and neck squamous cell carcinomas HNSCC from potentially premalignant lesions (PPOLS) to malignancy lymph node metastases. Likely pathological mutations predominantly involved a relatively small set genes reported previously ( TP53 , KMT2D CDKN2A PIK3CA NOTCH1 FAT1 ) but also other predicted cancer drivers MGA PABPC3 NR4A2 NCOR1 MACF1 ). Notably, all these arise early are present PPOLs. The most frequent genetic changes,...
BACKGROUNDDICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions. Other susceptibility genes for familial forms of MNG likely exist.METHODSWhole-exome sequencing a kindred early-onset schwannomatosis was followed by investigation germline pathogenic variants that fully segregated disease. Genome-wide analyses were performed on 13 tissue samples from nonfamilial DGCR8-E518K-positive...
Nontoxic multinodular goiter (MNG) occurs frequently, but its genetic etiology is not well established. Familial MNG and occurring with ovarian Sertoli-Leydig cell tumor are associated germline DICER1 mutations. We recently identified second somatic ribonuclease (RNase) IIIb mutations in two MNGs.The objective of the study was to investigate occurrence mutational clonality MNG.MNGs from 15 patients (10 five without mutations) were selected based on tissue availability.Core biopsies/scrapings...
Sarcomas are rare and heterogeneous cancers. We assessed the contribution of DICER1 mutations to sarcoma development. The coding region was sequenced in 67 sarcomas using a custom Fluidigm Access Array. RNase III domains were Sanger six additional identify hotspot variants. median age diagnosis 45.7 years (range: 3 months 87.4 years). A recurrent embryonal rhabdomyosarcoma (ERMS) broad ligament, first diagnosed at 23 years, harboured biallelic pathogenic somatic variants (1 truncating 1 IIIb...
Background : Development of a mature organism from single cell requires series important morphological changes, which is in part regulated by alternative splicing. In this article, we report the expression Esrp1 during early mouse embryogenesis, splicing factor implicated epithelial to mesenchymal transitions. Results By qRT‐PCR , find higher and Esrp2 placenta compared embryos. We also correlation between several known target exons. Using situ RNA hybridization show that while ubiquitous...
Not all familial ovarian cancer (OC) cases are explained by pathogenic germline variants in known risk genes. A candidate gene approach involving DNA repair pathway genes was applied to identify rare recurring OC not associated with from a population exhibiting genetic drift. Whole exome sequencing (WES) data of 15 13 families tested negative for were investigated 468 Filtering and prioritization criteria WES select top candidates further analyses. Candidates genotyped ancestry defined study...
Abstract Background Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function homologous recombination (HR) DNA, could involve other DNA repair pathway genes. Methods Whole exome sequencing was used to identify rare HR genes a variant negative OC family French Canadian (FC) ancestry, population exhibiting genetic drift. cancer-free individuals from FC non-FC populations were investigated for carrier frequency...
FANCI was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers c.1813C>T; p.L605F in OC families. Here, we aimed to investigate molecular characteristics FANCI, they have not been described context cancer. We first investigated germline landscape two sisters with discovery family (F1528) re-affirm plausibility this candidate. As did find other conclusive candidates, then performed approach identify variants genes involved protein...
Abstract Ovarian and endometrial cancers come within the top-4 for incident as well deaths in North American women. Cure rates have not improved 30 years high-grade subtypes continue to be diagnosed Stage III/IV. Attempts at early diagnosis failed because cancer cells exfoliate metastasize while primary is small undetectable by existing tests based on imaging blood-based tumor markers. DOvEEgene (Detecting Endometrial Early using genomics) a genomic uterine pap test developed McGill team...
Background: Detecting pathogenic intronic variants resulting in aberrant splicing remains a challenge routine genetic testing. We describe germline whole-exome sequencing (WES) analyses and apply silico predictive tools of familial ovarian cancer (OC) cases reported clinically negative for BRCA1 BRCA2 variants. Methods: WES data from 27 OC 53 sporadic early-onset were analyzed or BRCA2. carriers 10 other predisposing genes. Loss heterozygosity analysis was performed on tumor DNA variant...
To identify candidate variants in RAD51C and RAD51D ovarian cancer (OC) predisposing genes by investigating French Canadians (FC) exhibiting unique genetic architecture. Candidates were identified whole exome sequencing analysis of 17 OC families 53 early-onset cases. Carrier frequencies determined the 100 or HBOC families, 438 sporadic cases 1025 controls. Variants unknown function assayed for their biological impact and/or cellular sensitivity to olaparib. c.414G>C;p.Leu138Phe...
Objective We previously identified a pathogenic germline DICER1 variant in child with transposition of the great arteries who was member family syndrome. In view report linking Dicer1 knockout murine cardiomyocytes to cardiac outflow defects, we investigated involvement arteries. Design used Fluidigm access array followed by next generation sequencing screen for variants coding exons, their exon/intron boundaries and 3′ untranslated region patient DNA. Cases Germline DNA collected from 129...