Erratum: Genomic landscape of high-grade meningiomas

Bi, Wenya Linda; Greenwald, Noah F.; Abedalthagafi, Malak; Wala, Jeremiah A.; Gibson, Will J.; Agarwalla, Pankaj K.; Horowitz, Peleg; Schumacher, Steven E.; Esaulova, Ekaterina; Yu, Mei; Chevalier, Aaron; Ducar, Matthew; Thorner, Aaron R.; Hummelen, Paul Van; Stemmer‐Rachamimov, Anat; Artyomov, Maksym; Al‐Mefty, Ossama; Dunn, Gavin P.; Santagata, Sandro; Dunn, Ian F.; Beroukhim, Rameen

doi:10.1038/s41525-017-0023-6

Cited by 18 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20,21 The incidence of 22q LOH increases with WHO grade, with a 50% prevalence in WHO grade I tumors and 75-85% prevalence in WHO grades II and III tumors. 21,22 Deletion of chromosome 1p is the second most common CNA identified and is mainly associated with higher WHO grade. 21,23 Other recurrent chromosomal aberrations observed in meningiomas include loss of 4p, 6q, 7p, 9p, 10q, 11p, 14q, and 18q.…”

Section: Copy Number Alterationsmentioning

confidence: 99%

“…21,23,24,[26][27][28][29][30][31][32] Interestingly, grade I meningiomas with a greater burden of genomic disruption overall, and specifically 1p deletion, have a higher likelihood of progression and recurrence, lending evidence that there are genomic factors not captured by histopathological grade that can inform on the clinical behavior of meningiomas. 22,30,33 Additional evidence comes from findings of losses of chromosomes 1, 14, and 22 being more prevalent in recurrent and progressive tumors than de novo high-grade meningiomas. 33,34 Although profiling the CNAs in meningiomas provides valuable information regarding propensity for an aggressive clinical course, whether these alterations remain independently prognostic after controlling for more newly discovered molecular alterations discussed in sections to follow remains unknown, and indicates the need for more studies that utilize integrative approaches employing multiple "omics" platforms to compare and weigh the prognostic importance of genomic alterations.…”

Section: Copy Number Alterationsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular and translational advances in meningiomas

et al. 2019

Self Cite

View full text Add to dashboard Cite

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

show abstract

Section: Copy Number Alterationsmentioning

confidence: 99%

Section: Copy Number Alterationsmentioning

confidence: 99%

Molecular and translational advances in meningiomas

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Higher-grade meningiomas do appear to harbor mutations that are predicted to be neoantigens, and therefore immunotherapy may play a larger role in highergrade tumors. 119…”

Section: Potential Molecular Targetsmentioning

confidence: 99%

Advances in multidisciplinary therapy for meningiomas

et al. 2019

Self Cite

View full text Add to dashboard Cite

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.

show abstract

“…However, more data have accumulated regarding alterations in genes not previously implicated in meningiomas that appear to delineate subsets of progressive meningiomas with unfavorable clinical prognoses. These aberrations include promoter mutations and rearrangements of TERT , and inactivating mutations in BAP1 , PBRM1 , ARID1A , and SMARCE1 as well as focal deletions of the dystrophin gene ( DMD ) [ 2 , 3 , 14 , 19 – 21 , 28 , 33 , 41 ]. Mutations in some of these genes are enriched in tumors with distinct histologic features such as SMARCE1 in clear cell meningioma, and BAP1 and PBRM1 in rhabdoid and papillary meningiomas, respectively [ 33 , 36 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Distinct genomic subclasses of high-grade/progressive meningiomas: NF2-associated, NF2-exclusive, and NF2-agnostic

Williams

Santagata

Wakimoto

et al. 2020

acta neuropathol commun

Self Cite

View full text Add to dashboard Cite

Background Genomic studies of high-grade/progressive meningiomas have reported a heterogeneous mutation spectrum, identifying few recurrently mutated genes. Most studies have been underpowered to detect genomic subclasses of aggressive meningiomas due to relatively small number of available samples. Here, we present a genomic survey of one of the largest multi-institutional cohorts of high-grade/progressive meningiomas to date. Methods 850 high-grade/progressive meningiomas, including 441 WHO grade 2 and 176 WHO grade 3 meningiomas and 220 progressive WHO grade 1 meningiomas, were tested as part of a clinical testing program by hybridization capture of 406 cancer-related genes to detect base substitutions, indels, amplifications, deletions, and rearrangements. Information from pathology reports, histopathology review, and patient clinical data was assessed. Results Genomic analyses converged to identify at least three distinct patterns of biologically-aggressive meningiomas. The first and most common contained NF2-mutant tumors (n = 426, 50%), was associated with male sex (64.4% %, p = 0.0001) and often harbored additional mutations in CDKN2A/B (24%), and the chromatin regulators ARID1A (9%), and KDM6A (6%). A second group (NF2-agnostic) featured TERT promoter (TERTp; n = 56) or TP53 mutations (n = 25) and were either NF2-mutant or wild-type, and displayed no association with either sex (p = 0.39). The remaining group generally lacked NF2 mutations, and accounted for 40% of the cases—with three subgroups. One consistent primarily of grade 3 lesions harboring alterations in chromatin regulators BAP1 (n = 22) or PBRM1 (n = 16). A second subgroup contained AKT1 (n = 26), PIK3CA (n = 14) and SMO (n = 7) mutant skull-based meningiomas, and a third mixed subgroup included 237 meningiomas with a heterogeneous spectrum of low frequency and non-recurrent alterations. Conclusions Our findings indicate that the patterns of genomic alterations in high-grade/progressive meningiomas commonly group into three different categories. The most common NF2-associated canonical group frequently harbored CDKN2A/B alterations, which is potentially amenable to targeted therapies. An NF2-agnostic group harbored frequent TERTp and TP53 mutations. The final subclass, distinct from the canonical NF2 mutant associated pathway, was partly characterized by BAP1/PBRM1 alterations (rhabdoid/papillary histology) or skull-base disease. Overall, these data increase our understanding of the pathobiology of high-grade/progressive meningiomas and can guide the design of clinical trials. IRB approval status Reviewed and approved by Western IRB; Protocol No. 20152817.

show abstract

Erratum: Genomic landscape of high-grade meningiomas

Abstract: A correction to this article has been published and is linked from the HTML version of this article.

Cited by 18 publications

References 0 publications

Molecular and translational advances in meningiomas

Molecular and translational advances in meningiomas

Advances in multidisciplinary therapy for meningiomas

Distinct genomic subclasses of high-grade/progressive meningiomas: NF2-associated, NF2-exclusive, and NF2-agnostic

Contact Info

Product

Resources

About