scholarly journals HGG-11. HIGH-GRADE GLIOMAS IN ADOLESCENTS AND YOUNG ADULTS HIGHLIGHT HISTOMOLECULAR DIFFERENCES WITH THEIR ADULT AND PAEDIATRIC COUNTERPARTS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii345-iii346
Author(s):  
Alexandre Roux ◽  
Johan Pallud ◽  
Raphaël Saffroy ◽  
Myriam Edjlali-Goujon ◽  
Marie-Anne Debily ◽  
...  
Keyword(s):  
Young Adults ◽  
Molecular Techniques ◽  
Adolescents And Young Adults ◽  
High Grade ◽  
Who Grade ◽  
Targeted Next Generation Sequencing ◽  
Integrated Diagnosis ◽  
Idh Mutations ◽  
Specific Subgroup ◽  
High Grade Gliomas

Abstract BACKGROUND Considering that paediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). METHODS We performed a multicentric retrospective study of 112 AYAs from adult and paediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyse their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25-years, histopathological HGG diagnosis, available clinical data, pre-operative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next generation sequencing, whole exome sequencing and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 WHO classification. RESULTS Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of paediatric-subtypes (Histone H3-mutants, 40%) but also adult-subtypes (IDH-mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH-mutant and 1p/19q co-deleted and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, the non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. CONCLUSIONS HGGs in AYAs could benefit from a more personalized neuro-oncological management, driven by molecular subtyping rather than age group. Collaborative efforts are needed from paediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

scholarly journals High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts

2020 ◽  
Vol 22 (8) ◽  
pp. 1190-1202 ◽  
Author(s):  
Alexandre Roux ◽  
Johan Pallud ◽  
Raphaël Saffroy ◽  
Myriam Edjlali-Goujon ◽  
Marie-Anne Debily ◽  
...  
Keyword(s):  
Young Adults ◽  
Molecular Techniques ◽  
Adolescents And Young Adults ◽  
World Health ◽  
High Grade ◽  
Who Grade ◽  
Targeted Next Generation Sequencing ◽  
Integrated Diagnosis ◽  
Idh Mutations ◽  
High Grade Gliomas

Abstract Background Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). Methods We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. Results Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. Conclusions HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas

2012 ◽  
Vol 108 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Tareq A. Juratli ◽  
Matthias Kirsch ◽  
Katja Robel ◽  
Silke Soucek ◽  
Kathrin Geiger ◽  
...  
Keyword(s):  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Idh Mutations ◽  
Grade Ii ◽  
High Grade Gliomas

scholarly journals MPTH-06BRAFV600E MUTATION IN HIGH GRADE GLIOMAS OF CHILDREN AND YOUNG ADULTS

2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v139.1-v139
Author(s):  
Sridhar Epari ◽  
Hetakshi Kurani ◽  
Tejpal Gupta ◽  
Girish Chinnaswamy ◽  
Jayant Sastri Goda ◽  
...  
Keyword(s):  
Young Adults ◽  
High Grade ◽  
Children And Young Adults ◽  
High Grade Gliomas

scholarly journals Potential CanonicalWntPathway Activation in High-Grade Astrocytomas

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Rebecca Schüle ◽  
Christine Dictus ◽  
Benito Campos ◽  
Feng Wan ◽  
Jörg Felsberg ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Luciferase Reporter ◽  
High Grade ◽  
Luciferase Reporter Gene ◽  
Protein Truncation Test ◽  
Who Grade ◽  
Transcriptional Cofactors ◽  
Pathway Activation ◽  
Gene Assay ◽  
High Grade Gliomas

Aberrantwntpathway activation through cytoplasmic stabilization ofβ-catenin is crucial for the development of various human malignancies. In gliomagenesis, the role of canonical (i.e.,β-catenin-dependent) signalling is largely unknown. Here, we studied canonicalwntpathway activation in 15 short-term cultures from high-grade gliomas and potential pathomechanisms leading to cytoplasmicβ-catenin accumulation. Furthermore, we assessed the prognostic relevance ofβ-catenin expression in a tissue microarray comprising 283 astrocytomas. Expression ofβ-catenin, its transcriptional cofactors TCF-1 and TCF-4 as well as GSK-3βand APC, constituents of theβ-catenin degradation complex was confirmed by RT-PCR in all cultures. A cytoplasmicβ-catenin pool was detectable in 13/15 cultures leading to some transcriptional activity assessed by luciferase reporter gene assay in 8/13. Unlike other malignancies, characteristic mutations ofβ-catenin and APC leading to cytoplasmic stabilization ofβ-catenin were excluded by direct sequencing or protein truncation test. In patient tissues,β-catenin expression was directly and its degradation product's (β-catenin-P654) expression was inversely correlated with WHO grade. Increasedβ-catenin expression and lowβ-catenin-P654 expression were associated with shorter survival. Altogether, we report on potential canonicalwntpathway activation in high-grade gliomas and demonstrate thatβ-catenin expression in astrocytomas is associated with increased malignancy and adverse outcome.

scholarly journals Global trends in survival from brain tumours in adolescents and young adults: a systematic review.

2019 ◽  
Author(s):  
Fabio Girardi ◽  
Claudia Allemani ◽  
Michel P Coleman
Keyword(s):  
Systematic Review ◽  
Young Adults ◽  
Brain Tumours ◽  
Time Trends ◽  
Population Based ◽  
Adolescents And Young Adults ◽  
Who Grade ◽  
Middle Income ◽  
Middle Income Countries ◽  
Astrocytic Tumours

Abstract Background Brain tumours represent an important cause of cancer-related death in adolescents and young adults. Most are diagnosed in low-income and middle-income countries. We aimed to conduct the first systematic review of time trends and geographical variation in survival in this age group. Methods We included observational studies describing population-based survival from astrocytic tumours in patients aged 15-39 years. We queried six electronic databases from database inception to 30 September 2018. This review is registered with PROSPERO, number CRD42018111981. Results Among 5,245 retrieved records, 20 studies fulfilled the inclusion criteria. Only one study was partly conducted in middle-income countries. Five-year survival from astrocytoma (broad morphology group) varied between 48% and 71% (1973-2004), without clear trends or geographic differences. Adolescents with astrocytoma had better outcomes than young adults, but survival values were similar when non-malignant tumours were excluded. During 2002-2007, five-year survival for WHO grade I-II tumours was in the range 75-93% in England, Germany, and the US, but lower in South-Eastern Europe (59%). Five-year survival for anaplastic astrocytoma varied between 40% and 55% (2002-2007). Five-year survival from glioblastoma was in the range 15-23% (1991-2009). Conclusions Survival from astrocytic tumours remained somewhat steady over time, with little change between 1973 and 2009. Survival disparities were difficult to examine, because nearly all the studies were conducted in affluent countries. Studies often adopted the International Classification of Childhood Cancer, which, however, did not allow to accurately describe variation in survival. Larger studies are warranted, including under-represented populations and providing more recent survival estimates. Keywords Population-based survival, brain tumours, adolescents, young adults, time trends.

DNA hydroxymethylation in high-grade gliomas

2021 ◽  
Author(s):  
Angelika Stapińska-Syniec ◽  
Marta Grabiec ◽  
Marcin Rylski ◽  
Albert Acewicz ◽  
Michał Sobstyl
Keyword(s):  
Regulation Of Gene Expression ◽  
Epigenetic Mechanism ◽  
High Grade ◽  
Who Grade ◽  
Dna Hydroxymethylation ◽  
Current State ◽  
Survival Estimation ◽  
High Grade Gliomas ◽  
Tet Enzymes

Background and Study Aims Since the new WHO classification of nervous system tumors (2016 revised 4th edition) has been released, gliomas are classified depending on molecular and genetic markers in connection with histopathology, instead of histopathology itself as it was in the previous classification. Over the last years, epigenetic analysis has taken on increased importance in the diagnosis and treatment of different cancers. Multiple studies confirmed that DNA methylation and hydroxymethylation play an important role in the regulation of gene expression during carcinogenesis. In this review, we aim to present the current state of knowledge on DNA hydroxymethylation in human high-grade gliomas (WHO grade III and IV). Results The correlation of DNA hydroxymethylation and survival in glioblastoma patients was evaluated by different studies. The majority of them showed that the expression of 5-hydroxymethylcytosine (5-hmC) and Ten-eleven translocation (TET) enzymes were significantly reduced, sometimes almost undetectable in high-grade gliomas in comparison with the control brain. A decreased level of 5-hmC was associated with poor survival in patients, but high expression of the TET3 enzyme was related to a better prognosis for GBM patients. This points to the relevance of DNA hydroxymethylation in molecular diagnostics of human gliomas, including survival estimation or differentiating patients in terms of response to the treatment. Conclusion Future studies may shed some more light on this epigenetic mechanism involved in the pathogenesis of human high-grade gliomas and help to develop new targeted therapies.

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