Differential newborn DNA methylation among individuals with complex congenital heart defects and childhood lymphoma
Birth Defects Res. 2022 Oct 13. doi: 10.1002/bdr2.2105. Online ahead of print. ABSTRACT BACKGROUND: There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on “CHD-lymphoma” associations. […]
Dormant SOX9-positive cells facilitate MYC-driven recurrence of medulloblastoma
Cancer Res. 2022 Oct 11:CAN-22-2108. doi: 10.1158/0008-5472.CAN-22-2108. Online ahead of print. ABSTRACT Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription […]
Dispatches from Biotech beginning BeginNGS: Rapid newborn genome sequencing to end the diagnostic and therapeutic odyssey
Am J Med Genet C Semin Med Genet. 2022 Oct 11. doi: 10.1002/ajmg.c.32005. Online ahead of print. ABSTRACT In this Dispatch from Biotech, we briefly review the urgent need for extensive expansion of newborn screening (NBS) by genomic sequencing, and the reasons why early attempts had limited success. During the next decade transformative developments will […]
Approaches to long-read sequencing in a clinical setting to improve diagnostic rate
Sci Rep. 2022 Oct 9;12(1):16945. doi: 10.1038/s41598-022-20113-x. ABSTRACT Over the past decade, advances in genetic testing, particularly the advent of next-generation sequencing, have led to a paradigm shift in the diagnosis of molecular diseases and disorders. Despite our present collective ability to interrogate more than 90% of the human genome, portions of the genome have […]
Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors
J Immunother Cancer. 2022 Sep;10(9):e004450. doi: 10.1136/jitc-2021-004450. ABSTRACT BACKGROUND: Pediatric brain tumors are the leading cause of cancer death in children with an urgent need for innovative therapies. Glypican 2 (GPC2) is a cell surface oncoprotein expressed in neuroblastoma for which targeted immunotherapies have been developed. This work aimed to characterize GPC2 expression in pediatric […]
“A novel serum extracellular vesicle protein signature to monitor glioblastoma tumor progression”
Int J Cancer. 2022 Aug 27. doi: 10.1002/ijc.34261. Online ahead of print. ABSTRACT Detection of tumor progression in patients with glioblastoma remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of patients with glioblastoma. In this study, we evaluated the potential of serum-derived EVs from glioblastoma patients […]
A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases
Am J Hum Genet. 2022 Aug 18:S0002-9297(22)00355-X. doi: 10.1016/j.ajhg.2022.08.003. Online ahead of print. ABSTRACT Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it […]
Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huët anomaly
Am J Hum Genet. 2022 Aug 23:S0002-9297(22)00360-3. doi: 10.1016/j.ajhg.2022.08.008. Online ahead of print. ABSTRACT The transmembrane protein TMEM147 has a dual function: first at the nuclear envelope, where it anchors lamin B receptor (LBR) to the inner membrane, and second at the endoplasmic reticulum (ER), where it facilitates the translation of nascent polypeptides within the […]
Subgroup-Enriched Pathways and Kinase Signatures in Medulloblastoma Patient-Derived Xenografts
J Proteome Res. 2022 Aug 17. doi: 10.1021/acs.jproteome.2c00203. Online ahead of print. ABSTRACT Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MB is classified into four primary molecular subgroups: wingless (WNT), sonic hedgehog (SHH), Group 3 (G3), and Group 4 (G4), and further genomic and proteomic subtypes have been reported. Subgroup heterogeneity and […]
The long non-coding RNA SPRIGHTLY and its binding partner PTBP1 regulate exon 5 skipping of SMYD3 transcripts in group 4 medulloblastomas
Neurooncol Adv. 2022 Aug 2;4(1):vdac120. doi: 10.1093/noajnl/vdac120. eCollection 2022 Jan-Dec. ABSTRACT BACKGROUND: Although some of the regulatory genes, signaling pathways, and gene regulatory networks altered in medulloblastomas (MB) are known, the roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are poorly described. Here we report that the lncRNA SPRIGHTLY (SPRY4-IT1) gene is upregulated in […]