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Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors

ABSTRACT: Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors

PROVIDER: PRJNA998073 | ENA |

REPOSITORIES: ENA

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Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors

Project description:Long non-coding RNAs (lncRNAs) play an important role in gene regulation and contribute to tumorigenesis. While pan-cancer studies of lncRNA expression have been performed for adult malignancies, the lncRNA landscape across pediatric cancers remains largely uncharted. Here, we curated RNA sequencing data for 1,044 pediatric leukemia and extra-cranial solid tumors and integrated paired tumor whole genome sequencing and epigenetic data in relevant cell line models to explore lncRNA expression, regulation, and association with cancer. A total of 2,657 lncRNAs were robustly expressed across six pediatric cancers, including 1,142 exhibiting histotype-elevated expression. DNA copy number alterations contributed to lncRNA dysregulation at a proportion comparable to protein coding genes. Application of a multi-dimensional framework to identify and prioritize lncRNAs impacting gene networks revealed that lncRNAs dysregulated in pediatric cancer are associated with proliferation, metabolism, and DNA damage hallmarks. Analysis of upstream regulation via cell-type specific transcription factors further implicated distinct histotype-elevated and developmental lncRNAs. Integration of these analyses prioritized lncRNAs for experimental validation, and silencing of TBX2-AS1, the top-prioritized neuroblastoma-specific lncRNA, resulted in significant growth inhibition of neuroblastoma cells, confirming the computational predictions. Taken together, these data provide a comprehensive characterization of lncRNA regulation and function in pediatric cancers and pave the way for future mechanistic studies.

2023-07-31 | GSE238166 | GEO

Methylation data of pediatric B-cell acute leukemias

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Immuno-Transcriptomic Profiling Identifies Actionable Alterations in Pediatric Solid Malignancies

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Transcription profiling of human pediatric solid tumor cell lines

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2008-06-16 | E-GEOD-8596 | biostudies-arrayexpress

whole genome shallow sequencing of ctDNA from pediatric solid tumors

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An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies

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The landscape of somatic alterations in epigenetic genes across 21 pediatric cancers

Project description:As a part of the St Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project (PCGP), we adapted deep sequencing technologies and have sequenced 1025 tumor samples from 21 diseases covering brain, solid tumors and leukemias. We analyzed the genomic DNA sequences, copy number variations and structural rearrangements of 633 genes whose proteins are involved in epigenetic machineries, including those that covalently modify DNA and histones, and structurally reorder chromatin. To examine gene expression level of mutated histone genes, we analyzed gene expression in a group of 40 non-ETP T-lineage ALL samples using Affymetrix GeneChip HT HG-U133+ PM arrays (including 37 samples deposited in GSE28703 and 3 additional arrays not studied previously). The results provide us the knowledge of potential therapeutic targets for pediatric cancer treatment and improvement of personalized therapy. Gene expression profiling was performed on 40 non ETP T-lineage acute lymphoblastic leukemia samples. No control or reference samples were included.

2013-12-31 | E-GEOD-43209 | biostudies-arrayexpress

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