ABSTRACT
Purpose Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. Methods We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269). Results More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls with longer survival positively correlated with XIST expression. Conclusions The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers (AU)
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Brain Neoplasms/diagnosis , Glioma/diagnosis , Transcriptome , Brain Neoplasms/metabolism , Brain Neoplasms/genetics , Glioma/genetics , Glioma/metabolism , Biomarkers, Tumor/metabolism , Magnetic Resonance Imaging , MicroRNAs/metabolism , Astrocytoma/metabolism , RNA, Long Noncoding/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. METHODS: We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269). RESULTS: More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls' with longer survival positively correlated with XIST expression. CONCLUSIONS: The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers.
Subject(s)
Biomarkers, Tumor/metabolism , Brain Stem Neoplasms/diagnosis , Diffuse Intrinsic Pontine Glioma/diagnosis , RNA, Untranslated/metabolism , Transcriptome , Adolescent , Age Factors , Alternative Splicing , Astrocytoma/metabolism , Brain Neoplasms/metabolism , Brain Stem Neoplasms/diagnostic imaging , Brain Stem Neoplasms/genetics , Brain Stem Neoplasms/mortality , Child , Child, Preschool , Databases, Genetic , Diffuse Intrinsic Pontine Glioma/diagnostic imaging , Diffuse Intrinsic Pontine Glioma/genetics , Diffuse Intrinsic Pontine Glioma/mortality , Down-Regulation , Female , Humans , Infant , Magnetic Resonance Imaging , Male , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , RNA, Small Nucleolar/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sex Factors , Up-RegulationABSTRACT
Submicroscopic duplications in the Miller-Dieker critical region have been recently described as new genomic disorders. To date, only a few cases have been reported with overlapping 17p13.3 duplications in this region. Also, small deletions that affect chromosome region 10p14âpter are rarely described in the literature. In this study, we describe, to our knowledge for the first time, a 5-year-old female patient with intellectual disability who has an unbalanced 10;17 translocation inherited from the father. The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes. The patient's karyotype was established as 46,XX.arr 10p15.3p15.1(138,206-4,574,436)x1,17p13.3(87,009-3,312,600)x3. Because our patient exhibits a combination of 2 imbalances, she has phenotypic features of both chromosome abnormalities, which have been reported separately. Interestingly, the majority of patients who carry the deletion 10p have visual and auditory deficiencies that are attributed to loss of the GATA3 gene. However, our patient also presents severe hearing and visual problems even though GATA3 is present, suggesting the involvement of different genes that affect the development of the visual and auditory systems.
