Alpha thalassemia/mental retardation syndrome X-linked, the alternative lengthening of telomere phenotype, and gliomagenesis: Current understandings and future potential

Jenny He, Alireza Mansouri, Sunit Das

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Gliomas are the most common primary malignant brain tumor in humans. Lower grade gliomas are usually less aggressive but many cases eventually progress to a more aggressive secondary glioblastoma (GBM, WHO Grade IV), which has a universally fatal prognosis despite maximal surgical resection and concurrent chemo-radiation. With the identification of molecular markers, however, there is promise for improving diagnostic and therapeutic strategies. One of the key molecular alterations in gliomas is the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, which is frequently mutated. One-third of pediatric GBM cases are also found to have the ATRX mutation and the genetic signatures are different from adult cases. The exact role of ATRX mutations in gliomagenesis, however, is unclear. In this review, we describe the normal cellular function of the ATRX gene product followed by consequences of its dysfunction. Furthermore, its possible association with the alternative lengthening of telomeres (ALT) phenotype is outlined. Lastly, therapeutic options potentiated through a better understanding of ATRX and the ALT phenotype are explored.

Original languageEnglish (US)
Article number322
JournalFrontiers in Oncology
Volume7
Issue numberJAN
DOIs
StatePublished - Jan 8 2018

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Telomere Homeostasis
Glioma
alpha-Thalassemia
X-Linked Genes
Phenotype
Intellectual Disability
Mutation
Glioblastoma
Brain Neoplasms
Radiation
Pediatrics
Therapeutics
ATR-X syndrome

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Alpha thalassemia/mental retardation syndrome X-linked, the alternative lengthening of telomere phenotype, and gliomagenesis: Current understandings and future potential",
abstract = "Gliomas are the most common primary malignant brain tumor in humans. Lower grade gliomas are usually less aggressive but many cases eventually progress to a more aggressive secondary glioblastoma (GBM, WHO Grade IV), which has a universally fatal prognosis despite maximal surgical resection and concurrent chemo-radiation. With the identification of molecular markers, however, there is promise for improving diagnostic and therapeutic strategies. One of the key molecular alterations in gliomas is the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, which is frequently mutated. One-third of pediatric GBM cases are also found to have the ATRX mutation and the genetic signatures are different from adult cases. The exact role of ATRX mutations in gliomagenesis, however, is unclear. In this review, we describe the normal cellular function of the ATRX gene product followed by consequences of its dysfunction. Furthermore, its possible association with the alternative lengthening of telomeres (ALT) phenotype is outlined. Lastly, therapeutic options potentiated through a better understanding of ATRX and the ALT phenotype are explored.",
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T2 - Current understandings and future potential

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AU - Mansouri, Alireza

AU - Das, Sunit

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N2 - Gliomas are the most common primary malignant brain tumor in humans. Lower grade gliomas are usually less aggressive but many cases eventually progress to a more aggressive secondary glioblastoma (GBM, WHO Grade IV), which has a universally fatal prognosis despite maximal surgical resection and concurrent chemo-radiation. With the identification of molecular markers, however, there is promise for improving diagnostic and therapeutic strategies. One of the key molecular alterations in gliomas is the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, which is frequently mutated. One-third of pediatric GBM cases are also found to have the ATRX mutation and the genetic signatures are different from adult cases. The exact role of ATRX mutations in gliomagenesis, however, is unclear. In this review, we describe the normal cellular function of the ATRX gene product followed by consequences of its dysfunction. Furthermore, its possible association with the alternative lengthening of telomeres (ALT) phenotype is outlined. Lastly, therapeutic options potentiated through a better understanding of ATRX and the ALT phenotype are explored.

AB - Gliomas are the most common primary malignant brain tumor in humans. Lower grade gliomas are usually less aggressive but many cases eventually progress to a more aggressive secondary glioblastoma (GBM, WHO Grade IV), which has a universally fatal prognosis despite maximal surgical resection and concurrent chemo-radiation. With the identification of molecular markers, however, there is promise for improving diagnostic and therapeutic strategies. One of the key molecular alterations in gliomas is the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, which is frequently mutated. One-third of pediatric GBM cases are also found to have the ATRX mutation and the genetic signatures are different from adult cases. The exact role of ATRX mutations in gliomagenesis, however, is unclear. In this review, we describe the normal cellular function of the ATRX gene product followed by consequences of its dysfunction. Furthermore, its possible association with the alternative lengthening of telomeres (ALT) phenotype is outlined. Lastly, therapeutic options potentiated through a better understanding of ATRX and the ALT phenotype are explored.

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