BCOR

Researchers from the Institute of Cancer Research (ICR) have identified a new treatment pathway for a rare set of childhood brain tumours known as gliomatosis cerebri. Published in the journal Neuro-Oncology and funded by the Rudy A Menon Foundation and the Ollie Young Foundation, the decade-long study could lead to more effective treatments to treat this set of conditions. Affecting approximately 100 people every year in the US, gliomatosis cerebri is a highly aggressive form of glioma that presents as a spider’s web of cancer threads that spread deep into the brain. No chemotherapy has proven to be effective when treating this form of brain cancer, which is almost impossible to remove with surgery and is difficult to treat with radiotherapy. Carried out by the High-Grade Glioma Working Group on behalf of the International Society for Paediatric Oncology Europe, researchers collected brain tissue samples to carry out the study involving 104 children and adolescents living with the disease. The team used tumour profiling to understand what molecules are driving cancer and was able to identify a molecular profile for gliomatosis cerebri. The results revealed two subtypes known as pedHGG_RTK2A/B and pedHGG_A/B, which were both associated with paediatric gliomatosis cerebri. In addition, researchers revealed that mutations in the epidermal growth factor receptor protein and the BCOR gene, along with rearrangements of chromosome 6, were the most common genetic features. Findings from the study could help researchers identify potential drug targets for this condition. Chris Jones, professor of childhood brain tumour biology, ICR, commented: “We demonstrated that gliomatosis cerebri tumours behave very aggressively and differ from other types of gliomas found in children. “Contrary to previous research, the… study has shown that there are distinct molecular and clinical features of gliomatosis cerebri and this provides evidence that it ought to be re-considered as a separate entity.” Co-founder of the Rudy A Menon Foundation, Vidhu Menon, said that this “research has led to significant progress” and “will become the cornerstone for further understanding and finding effective treatments for this disease globally”.

10 abstracts accepted for presentation at three top genetic conferences, focusing on topics ranging from Whole Genome and Whole Exome Sequencing to Carrier Screening and Non-Invasive Prenatal TestingHOUSTON, Oct. 02, 2023 (GLOBE NEWSWIRE) -- Baylor Genetics, a clinical diagnostic laboratory at the forefront of genetic testing, today announced its scientists and genetic counselors will present 10 research abstracts at three major upcoming conferences, including the National Organization for Rare Disorders (NORD) Breakthrough Summit, National Society of Genetic Counselors (NSGC) Annual Conference, and the American Society of Human Genetics (ASHG) Annual Meeting. “With our ongoing focus on scientific publications and presentations, Baylor Genetics continues to conduct and share meaningful research findings drawn from our collaboration with the Baylor College of Medicine and other partners so that we can advance the field of genetics and provide better answers for the patients and providers who rely on us,” said Christine Eng, M.D, Chief Medical Officer and Chief Quality Officer at Baylor Genetics. “These annual meetings are an important opportunity for researchers, clinicians, and lab professionals to come together with care teams to exchange knowledge and data that represent the latest insights in genetic testing and personalized care.” NORD Breakthrough Summit, October 15-17, Washington, D.C. The NORD Rare Diseases and Orphan Products Breakthrough Summit brings together more than 900 advocates, experts, and stakeholders to tackle pressing issues facing the rare disease community. Robert Rigobello, Manager of Medical Affairs at Baylor Genetics will present two accepted abstracts: “ACMG Secondary Findings: A Review of Patient Choices in Reporting” Summary: Baylor Genetics reviewed internal data, ordering and reporting practices for secondary findings on Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) tests from 15 US-based laboratories. Researchers found that despite guidance from the American College of Medical Genetics and Genomics (ACMG), there are inconsistencies in families’ selection for reporting secondary findings and significant variation in reporting practices among surveyed laboratories. The authors recommended consistent practice would be beneficial to providers and families. “A Case Report: BCOR-related Congenital Hypertrophy of the Retinal Pigment Epithelium” Summary: Whole exome sequencing revealed a variant in the BCOR gene, which led to a diagnosis of X-linked Microphthalmia, syndromic 2, a spectrum disorder which includes oculofaciocardiodental (OFCD) syndrome on a patient with multisystemic findings, including congenital hypertrophy of the retinal pigment epithelium (CHRPE). BCOR-associated CHRPE has only been reported a few times in literature, but cases suggest BCOR testing should be considered for patients with CHRPE who have additional findings consistent with a congenital anomaly syndrome. NSGC Annual Conference, October 17-21, Chicago The National Society of Genetic Counselors Annual Conference showcases advancements across the genetic counseling profession, to share knowledge of clinical and scientific best practices and insights into emerging research. Christina Settler, Vice President, Medical Affairs, and Carli Andrews, Medical Science Liaison at Baylor Genetics will present findings from three accepted abstracts. “ACMG Secondary Findings: A Review of Patient Choices in Reporting” Baylor Genetics reviewed internal data, ordering and reporting practices for secondary findings on WES and WGS tests from 15 US-based laboratories. Researchers found that despite guidance from ACMG, there are inconsistencies in families’ selection for reporting secondary findings and significant variation in reporting practices among the surveyed laboratories. The authors recommended consistent practice would be beneficial to providers and families. “When Symptoms Don’t Make Sense: The Power of Diagnostic Tools for Identifying Dual Diagnoses” Summary: Researchers performed a retroactive study of patients who had concurrent WES and chromosomal microarray analysis (CMA) tests ordered between 2018-2022. Fifteen patients had a dual diagnosis. For most (10), WES and CMA provided distinct diagnoses. “ACMG Secondary Findings: A Reporting Dilemma” Summary: Baylor Genetics reviewed the practices when returning secondary findings on WES and WGS tests from 15 US-based laboratories. These findings indicate there is no consistent reporting process for secondary findings on WES/WGS with 8 out of 15 labs issuing individual parental reports separate from the proband report. The practice of charging for additional reports and reporting of additional findings aside from secondary findings varied among the labs reviewed as well. ASHG Annual Meeting, November 1-5, Washington, D.C. The American Society of Human Genetics’ Annual Meeting brings together more than 8,000 scientists to discuss advances in the field. Baylor Genetics experts had five abstracts accepted for the annual event. These will be presented by Qin Sun, Ph.D., Senior Division Director of Biochemical Genetics at Baylor Genetics; Hongzheng Dai, Ph.D., Associate Clinical Director NGS/Molecular, Baylor Genetics; Matthew Chau, Fellow, Clinical Genomics, Baylor Genetics; Weimin Bi, Ph.D., Division Director, Cytogenetics, Baylor Genetics, and Janice Smith, Ph.D., Senior Clinical Director, Cytogenetics, Baylor Genetics. “Advancing Tay-Sachs Disease Carrier Screening: Insights from Combined Enzyme and Molecular Approaches” Summary: Researchers conducted a retrospective analysis of Tay Sachs disease carrier test results from the Baylor Genetics laboratory database. Findings highlight the potential value of including molecular testing for HEXA in carrier screening in combination with Hex A enzyme analysis. “Advancing Precision Diagnosis through Simultaneous Detection of Diverse Variant Types: Insights from Clinical Whole Genome Sequencing” Summary: Whole Genome Sequencing (WGS) offers healthcare providers the ability to test for many types of variants with one assay. This abstract summarizes the experience performing clinical WGS at Baylor Genetics to highlight its utility as a first-tier diagnostic test capable of detecting a spectrum of variant types. The review found up to 30% of patients with a diagnostic WGS finding related to phenotype would not have been captured by assays only focusing on SNV/indels. “Not Just One: The Utility of Whole Genome Sequencing for Making a Dual Molecular Diagnosis” Summary: Whole genome sequencing (WGS) offers a comprehensive solution for genetic investigation by capturing a wide range of genomic variations in a single test. Researchers performed a retrospective evaluation of WGS results at Baylor Genetics to look for multiple reportable molecular findings. Reportable multilocus findings were detected in 48 cases. “Prenatal CMA Using Exon-Level Coverage for 'Disease Gene' CNV Interrogations in the Era of Non-Invasive Prenatal Testing” Summary: This study investigated the role of prenatal chromosomal microarray analysis (CMA) in the era of non-invasive prenatal testing (NIPT) over the last 11 years at Baylor Genetics. Researchers found prenatal CMA remains essential for the detection of microdeletions/duplications because NIPT is limited in screening for submicroscopic copy number changes, and a diagnostic test such as CMA in follow up to NIPT results that are positive or at increased risk is important. “Products of Conception Analysis by Chromosomal Microarray: A Single Center Experience” Summary: Researchers reviewed data of products of conception (POC) via conventional chromosome analysis or chromosomal microarray (CMA). The data show CMA has an advantage over conventional chromosome analysis. To learn more about Baylor Genetics, come see us at ASHG (booth 1826), NSGC (booth 200) and NORD (booth 322), or visit baylorgenetics.com. About Baylor Genetics A pioneer of precision medicine for over 40 years, Baylor Genetics is a leading diagnostic genomics partner offering a full spectrum of clinically relevant genetic testing, including Whole Genome Sequencing, Whole Exome Sequencing, and focused panels. A joint venture of H.U. Group Holdings, Inc. and Baylor College of Medicine, which has the #1 NIH-funded Department of Molecular and Human Genetics, Baylor Genetics couples the fastest and most comprehensive precision diagnostics options with the support of genetic counselors to help clinicians and their patients avoid a lengthy diagnostic odyssey, guide medical management, and make sure no patient with a genetic disorder gets left behind. Its test menu spans from family planning, pregnancy, neonatal and pediatric testing, oncology, and specialized test options. Baylor Genetics is located in Houston’s Texas Medical Center and serves clients in 50 states and 16 countries.

Researchers at the Institute of Cancer Research (ICR) in London have discovered new inhibitors that block the action of a protein involved in driving several cancer types. According to the team, with further research, the compounds could be developed into drugs to treat a range of cancers. Initially discovered as a cancer-driving protein in B-cell lymphoma, B-cell lymphoma 6 (BCL6) has since been linked with an increasing number of blood cancers and solid tumours, including some forms of leukaemia, breast cancer and non-small cell lung cancer. The protein works by binding to hundreds of target genes, before switching them off by recruiting several different ‘co-repressor’ proteins. In the new study, published in the journal Scientific Reports , the team from the Centre for Cancer Drug Discovery at the ICR describe an integrated workflow that led to the discovery of the novel inhibitors of the BCL6 protein. The researchers used a combination of high throughput screening, multiple biophysical techniques, X-ray crystallography and cell-based methods to discover the novel compounds offering the potential to block the ability of BCL6 to switch off its target genes and kill cancer cells. “Identifying drug compounds that disrupt protein-protein interactions, such as the BCL6-corepressor interaction, has traditionally proved to be extremely challenging,” explained study leader Dr Rob van Montfort, who leads the Hit Discovery and Structural Design Team at the ICR, saying that the combination method used by the team meant they were able to “effectively discover several BCL inhibitors from multiple chemical series”. “It’s exciting to reach this stage, creating a shortlist of promising compounds and helping to improve them to the very potent and selective inhibitors we have published previously and that have the potential to move into the next phase of drug discovery,” he added. In November 2022, researchers from the ICR and the Royal Marsden NHS Foundation Trust revealed joint plans to create a new generation of treatments that target the ecosystems within the body supporting cancer. The five-year strategy aims to accelerate progress for cancer patients by leveraging the latest advances in scientific knowledge and technology to focus research on the cells, signals and immune responses in the tissue environment that nurtures tumours. The researchers will also employ artificial intelligence to design new ways to combine existing treatments and smart dosing strategies, with the aim of doubling the survival of patients with advanced cancer within a decade.