Kasmintan A. Schrader
A5024943747- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Genomics and Rare Diseases
- Pancreatic and Hepatic Oncology Research
- DNA Repair Mechanisms
- Ethics in Clinical Research
- Health Systems, Economic Evaluations, Quality of Life
- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Prostate Cancer Treatment and Research
- Nutrition, Genetics, and Disease
- Advanced Causal Inference Techniques
- Renal cell carcinoma treatment
- Genetic Associations and Epidemiology
- Renal and related cancers
- Helicobacter pylori-related gastroenterology studies
- COVID-19 and healthcare impacts
- Multiple and Secondary Primary Cancers
- Colorectal Cancer Treatments and Studies
- Cancer-related gene regulation
- Digestive system and related health
University of British Columbia
2016-2025
BC Cancer Agency
2016-2025
Pancreas Centre (Canada)
2019-2024
Canada's Michael Smith Genome Sciences Centre
2016-2023
McGill University
2023
Health Net
2023
University Health Network
2023
Molecular Oncology (United States)
2020-2022
University of the Fraser Valley
2020
Provincial Health Services Authority
2020
<h3>Importance</h3> E-cadherin (<i>CDH1</i>) is a cancer predisposition gene mutated in families meeting clinically defined hereditary diffuse gastric (HDGC). Reliable estimates of risk and spectrum germline mutation carriers are essential for management. For without<i>CDH1</i>mutations, genetic-based stratification has not been possible, resulting limited clinical options. <h3>Objectives</h3> To derive accurate breast risks in<i>CDH1</i>mutation determine if mutations other genes associated...
Tumor genetic sequencing identifies potentially targetable alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well.To estimate the burden identified through routine clinical tumor sequencing.Patients advanced cancer diagnoses eligible for studies targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal MSK-IMPACT, a 341-gene panel. We surveyed seen in...
<h3>Objective</h3> The purpose of this study was the clinical and pathological characterisation a new autosomal dominant gastric polyposis syndrome, adenocarcinoma proximal stomach (GAPPS). <h3>Methods</h3> Case series were examined, documenting GAPPS in three families from Australia, USA Canada. affected identified through referral to centralised genetics centres. <h3>Results</h3> report identifies features including predominant dysplastic fundic gland polyp histology, exclusive involvement...
Purpose: Recent studies have identified mutation signatures of homologous recombination deficiency (HRD) in over 20% breast cancers, as well pancreatic, ovarian, and gastric cancers. There is an urgent need to understand the clinical implications HRD signatures. Whereas BRCA1/2 mutations confer sensitivity platinum-based chemotherapies, it not yet clear whether can independently predict platinum response.Experimental Design: In this observational study, we sequenced tumor whole genomes (100×...
Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority approaches profile panels selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing analysis (WGTA) present an opportunity align a much larger proportion patients therapies.Samples from 570 with advanced metastatic diverse types enrolled in Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy...
The variant curation guidelines published in 2015 by the American College of Medical Genetics and Genomics Association for Molecular Pathology (ACMG/AMP) provided genetics community with a framework to assess pathogenicity; however, these rules are not gene specific. Germline pathogenic variants CDH1 cause hereditary diffuse gastric cancer lobular breast cancer, clinically challenging predisposition syndrome that often requires multidisciplinary team experts be properly managed. Given this...
Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline p. L349P mutation kindred affected by thrombocytopenia and ALL. A second N385fs was identified an unrelated characterized thrombocytopenia, secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from proband showed deletion of wild type with retention N385fs....
Next-generation sequencing (NGS) has enabled whole-exome and whole-genome of tumors for causative mutations, allowing more accurate targeting therapies. In the process tumor, comparisons to germline genome may identify variants associated with susceptibility cancer as well other hereditary diseases. Already, combination massively parallel selective capture approaches facilitated efficient simultaneous genetic analysis (multiplex testing) large numbers candidate genes. As field oncology...
Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson (HH) clinically severe variant DC patients also have cerebellar hypoplasia may present with immunodeficiency enteropathy. We discovered autosomal recessive mutation RTEL1, helicase critical telomeric functions, two unrelated families Ashkenazi Jewish (AJ)...
In Brief OBJECTIVE: To estimate the frequency of BRCA1 and BRCA2 germline mutations in women with nonmucinous epithelial ovarian carcinoma unselected for a family history breast or cancer. METHODS: From 2004 to 2009, undergoing surgical staging carcinoma, including fallopian tube primary peritoneal were invited participate tumor banking genetic counseling mutations. Pathology obtained by gynecologic oncology surgeon counselors reviewed. RESULTS: Of 131 fulfilling entry criteria, found 20%...
Sequencing tests assaying panels of genes or whole exomes are widely available for cancer risk evaluation. However, methods classification variants resulting from this testing not well studied. We evaluated the ability a variant-classification methodology based on American College Medical Genetics and Genomics (ACMG) guidelines to define rate mutations uncertain significance (VUS) in 180 medically relevant genes, including all ACMG-designated reportable non-cancer-associated individuals who...
Understanding the gene-specific risks for development of breast cancer will lead to improved clinical care those carrying germline mutations in predisposition genes. We sought detail spectrum and refine risk estimates known proposed susceptibility Targeted massively-parallel sequencing was performed identify copy number variants 26 or genes 2134 BRCA1/2-negative women with familial (proband a family history ovarian cancer) from largely European-Caucasian multi-institutional cohort....
Given the success of targeted agents in specific populations it is expected that some degree molecular biomarker testing will become standard care for many, if not all, cancers. To facilitate this, cancer centers worldwide are experimenting with "panel" sequencing selected mutations. Recent advances genomic technology enable generation genome-scale data sets individual patients. Recognizing risk, inherent panel sequencing, failing to detect meaningful somatic alterations, we sought establish...
Structural variants (SVs) may be an underestimated cause of hereditary cancer syndromes given the current limitations short-read next-generation sequencing. Here we investigated utility long-read sequencing in resolving germline SVs susceptibility genes detected through genome sequencing.Known or suspected deleterious were identified using Illumina across a cohort 669 advanced patients with paired tumor and transcriptome Candidate subsequently assessed by Oxford Nanopore sequencing.Nanopore...
There is emerging evidence about the predictive role of homologous recombination deficiency (HRD), but this less defined in gastrointestinal (GI) and thoracic malignancies. We reviewed whole genome (WGS) transcriptomic (RNA-Seq) data from advanced GI cancers Personalized OncoGenomics trial (NCT02155621) to evaluate HRD scores single base substitution (SBS)3, which associated with BRCA1/2 mutations potentially defective HRD. were calculated by sum loss heterozygosity, telomeric allelic...
Abstract The role for routine whole genome and transcriptome analysis (WGTA) poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles germline cancer predisposition variants in children adolescents with relapsed, refractory or malignancies who underwent WGTA matched sequencing. Seventy-nine participants a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are...
Thyroid cancer management is rapidly changing. The identification of actionable biomarkers through both germline and somatic testing are now an integral part directing patient management. However, deficiencies disparities within existing thyroid biomarker test approaches resulting in inconsistent application for care. An expert panel was convened to create consensus algorithms recommendations on patients diagnosed with medullary cancer, non-anaplastic follicular cell-derived or anaplastic...
<h3>Background</h3> Germline mutations in <i>CDH1</i> are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively families such condition. <h3>Method</h3> To determine if is a susceptibility gene for women without family history of cancer, germline DNA was analysed the presence 318 who were diagnosed before age 45 years or had and not known, known not, to be carriers <i>BRCA1</i> <i>BRCA2</i>. Cases ascertained through registries high-risk genetic...
Background A somatic mutation in the FOXL2 gene is reported to be present almost all (97%; 86/89) morphologically defined, adult-type, granulosa-cell tumors (A-GCTs). This c.402C>G changes a highly conserved cysteine residue tryptophan (p.C134W). It was also found minority of other ovarian malignant stromal tumors, but not benign or unrelated breast cancers. Methodology/Principal Findings Herein we studied cancers and cell lines for presence this mutation. We screened DNA from 752 epithelial...
We report a patient with clinical and molecular diagnosis of LEOPARD syndrome (LS) associated multiple granular cell tumors (MGCT). Bidirectional sequencing exons 7, 12, 13 the PTPN11 gene revealed T468M missense mutation in exon 12. This has been previously reported patients LS. To our knowledge, this is first MGCT molecularly characterized LS provides evidence linking (GCT) to Ras/mitogen‐activated protein (MAP) kinase pathway. propose that can be Analysis GCT from case tested negatively...