Medulloblastoma (MB), a central nervous system tumor that predominantly affects children, requires aggressive therapy in all cases. It frequently recurs as resistant to treatment and is associated with high morbidity and mortality. In addition, affected individuals often suffer from disorders secondary to therapy. About 20% of all childhood brain tumors are medulloblastomas (MBs) and in a recent single-cell sequencing study, using cells from the developing murine brain (cerebellum) revealed that different molecular subgroups of childhood cerebellar tumors reflect the transcription of cells from distinct, temporally restricted cerebellar lineage.
There are four major molecular subgroups MBs: wingless-type (WNT)-activated MB (10%; children and adults, associated with very good prognosis), sonic hedgehog (SHH)-activated MB (30%; intermediate prognosis; infants and adults), Group III MB (25%; poor prognosis; infants and children), and Group IV MB (35%; intermediate prognosis; children and adults). Unsurprisingly ongoing transcriptomic and genome-wide methylation studies are revealing even greater heterogeneity in these subgroups.
By applying machine-learning classification to publicly available 175 genome-wide transcriptomics (RNA-seq) and 742 Affymetrix microarray data sets, researchers have identified several subgroup-specific MB lncRNAs. Among them, lncRNA HLX2-7 was highly upregulated in Group III MBs compared to other groups.
These proposed studies will hope to provide insights into the interplay between HLX2-7 and its partner molecules and how these interactions are involved in normal early brain development, and how these mechanisms are altered in the development of malignant medulloblastomas. These studies also look to provide novel and general insights into how lncRNAs regulate cellular states through their interactions with target molecules. Ultimately, the data should pave the way for new lncRNA-based diagnostics and therapeutics for human medulloblastomas.