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SLIT2 constitutes a known tumour suppressor gene, which has not yet been implicated in the pathogenesis of primary central nervous system lymphoma (PCNSL). Performing exome sequencing on paired blood and tumour DNA samples from six treatment-naïve PCNSL patients, we identified novel SLIT2 variants (p.N63S, p.T590M, p.T732S) that were associated with shorter progression-free survival in our cohort and shorter overall survival in a large validation cohort of lymphoid malignancies from the cBio Cancer Genomics Portal. WNT- and NF-κB-reporter luciferase assays suggest detected alterations are loss-of-function variants. Given the possible prognostic implications, the role of SLIT2 in PCNSL pathogenesis and progression warrants further investigation.
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http://dx.doi.org/10.1111/bjh.17319 | DOI Listing |
Signal Transduct Target Ther
September 2025
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Essential tremor (ET) is a common neurological disease that is characterized by 4-12 Hz kinetic tremors of the upper limbs and high genetic heterogeneity. Although numerous candidate genes and loci have been reported, the etiology of ET remains unclear. A novel ET-related gene was initially identified in a five-generation family via whole-exome sequencing, and other variants were identified in 772 familial ET probands and 640 sporadic individuals via whole-genome sequencing.
View Article and Find Full Text PDFCell Genom
September 2025
Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance.
View Article and Find Full Text PDFAm J Hum Genet
September 2025
Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Department of Pediatrics and Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: erid
Fetal brain anomalies identified by prenatal ultrasound and/or magnetic resonance imaging represent a considerable healthcare burden with ∼1-2/1,000 live births. To identify the underlying etiology, trio prenatal exome sequencing or genome sequencing (ES/GS) has emerged as a comprehensive diagnostic paradigm with a reported diagnostic rate up to ∼32%. Here, we report five unrelated families with six affected individuals that presented neuroanatomical, craniofacial, and skeletal anomalies, all harboring rare, bi-allelic deleterious variants in SNAPIN, which encodes SNARE-associated protein.
View Article and Find Full Text PDFMol Biol Rep
September 2025
Cytogenetics and Molecular Genetics Lab, Pathology Unit, Medical Division (BARC Hospital), Bhabha Atomic Research Centre, Anushakti Nagar, Mumbai, India.
Background: Hearing loss (HL) is one of the most common congenital anomalies and is a complex etiologically diverse condition. Molecular genetic characterization of HL remains challenging owing to the high genetic heterogeneity. This study aimed to screen for potential disease-causing genetic variations in a cohort of Indian patients with congenital bilateral severe-to-profound sensorineural HL.
View Article and Find Full Text PDFGenet Med
September 2025
Institute for Clinical and Translational Science, University of California, Irvine, CA, USA.
Purpose: Advancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging technologies are now being deployed to address the remaining diagnostic gap.
Methods: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing.