Melissa Batts
A5052655525- Glioma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Hedgehog Signaling Pathway Studies
- Mechanisms of cancer metastasis
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- CNS Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Ocular Oncology and Treatments
- Kruppel-like factors research
- Mitochondrial Function and Pathology
- Ferroptosis and cancer prognosis
- Developmental Biology and Gene Regulation
St. Jude Children's Research Hospital
2022-2025
Abstract Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% G4 medulloblastoma). In contrast, highly similar SHH distinct diametrically opposed gain-of-function mutations copy number gains (20% Overexpression...
Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function 1 . As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase complex, KBTBD4 is recurrently mutated in medulloblastoma (MB) 2 , most common embryonal brain tumor children, and pineoblastoma 3 These impart gain-of-function induce degradation transcriptional corepressor CoREST 4 However, their mechanism action remains unresolved. Here, we elucidate mechanistic basis by which promote through...
Abstract BACKGROUND Pineoblastoma (PB) is a rare and aggressive childhood brain tumor with highly variable outcomes. PB diagnostically characterized by expression of the photoreceptor identity transcription factor CRX, while tumors can be further classified into molecular subgroups (PB-miRNA1, PB-miRNA2, PB-MYC/FOXR2, PB-RB1), each marked unique clinico-molecular features. However, developmental origins subgroup heterogeneity mechanisms governing malignancy remain unknown. METHODS We...
Abstract BACKGROUND Medulloblastoma (MB), an aggressive pediatric brain cancer, poses significant treatment challenges due to its complex disease biology, comprising a collection of discrete molecular subtypes that require different treatment. Although the genomics, transcriptomics, and epigenetic landscapes biologically distinct MB subgroups are well-annotated have contributed enhanced diagnostics risk stratification, intersection these layers with proteome remains poorly defined METHODS To...
Abstract BACKGROUND Germline loss-of-function (LOF) variants in Elongator complex protein 1 (ELP1) are the most prevalent predisposing genetic events observed medulloblastoma (MB), accounting for 30% of Sonic Hedgehog 3 subtype (SHH-3). Molecularly, ELP1-associated SHH-MBs acquire somatic PTCH1 mutations >80% cases, and universal loss-of-heterozygosity wild-type ELP1 alleles through loss chromosome-arm 9q, resulting their biallelic inactivation. Notably, germline LOF occurs mutually...
Abstract BACKGROUND Medulloblastoma (MB) is a highly malignant childhood cerebellar tumor comprising collection of molecularly and clinically distinct entities. Group 3 4-MB subgroups originate from overlapping progenitor pools the developing rhombic lip when neuronal differentiation hierarchies are subverted through somatic alterations. Mutations suspected to deregulate activity chromatin-modifying genes pervasive in 4-MB. However, molecular consequences these alterations remain largely...
Abstract Germline loss-of-function (LOF) variants in Elongator complex protein 1 (ELP1) are the most prevalent predisposing genetic events observed medulloblastoma (MB), accounting for 30% of Sonic Hedgehog 3 subtype (SHH-3). Molecularly, ELP1-associated SHH-MBs acquire somatic PTCH1 mutations >80% cases, and universal loss-of-heterozygosity wild-type ELP1 alleles through loss chromosome-arm 9q, resulting their biallelic inactivation. Notably, germline LOF occurs mutually exclusive...
Abstract Germline loss-of-function (LOF) mutations in Elongator complex protein 1 (ELP1) are found 15-20% of childhood SHH medulloblastoma (MB) and exceedingly rare non-SHH-MB or other cancers. ELP1 germline carriers that develop SHH-MB harbor frequent somatic PTCH1 universally sustain loss-of-heterozygosity the remaining allele through chromosome 9q deletion. functions as a scaffolding subunit is required for posttranscriptional modification tRNAs maintenance efficient translational...
Abstract Pineoblastoma (PB), a rare and aggressive brain tumor affecting children, presents with highly variable age distribution treatment outcome. Our recent bulk analyses of DNA methylation mutational landscapes uncovered four discrete PB molecular subgroups (PB-miRNA1, PB-miRNA2, PB-MYC/FOXR2, PB-RB), providing major advance in our understanding biological clinical heterogeneity. However, developmental origins subgroup heterogeneity mechanisms governing how specific genetic alterations...
Abstract Germline loss-of-function (LOF) variants in Elongator complex protein 1 (ELP1) are the most prevalent predisposing genetic events childhood medulloblastoma (MB). ELP1 germline carriers develop SHH-MBs that exhibit coincident somatic PTCH1 mutations and universal loss-of-heterozygosity of remaining allele through chromosome 9q deletion. The molecular, biochemical, cellular mechanisms by which ELP1/Elongator deficiency contribute to SHH-MB tumorigenesis remain largely unknown. Herein,...
Abstract Pineoblastoma (PB) is a rare and aggressive childhood brain tumor with highly variable age treatment-associated outcomes. Our recent bulk analyses of DNA methylation mutational landscapes uncovered four discrete PB molecular subgroups (PB-miRNA1, PB-miRNA2, PB-MYC/FOXR2, PB-RB), providing major advance in our understanding biological clinical heterogeneity. However, developmental origins subgroup heterogeneity mechanisms governing how specific genetic alterations promote malignancy...