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The Genomics of Glioblastoma
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The Genomics of Glioblastoma

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Neurogenomics".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 10271

Special Issue Editors

Dr. Cristian Scatena

E-Mail Website
Guest Editor
1. Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
2. Department of Oncology, Pisa University Hospital, 56126 Pisa, Italy
Interests: pathology; tumour microenvironment; molecular genetics; breast cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Pasqualetti

E-Mail Website
Guest Editor
Department of Oncology, University of Oxford, Oxford OX1 2JD, UK
Interests: radiation oncology; translational research; neuro-oncology; molecular genetics
Dr. Luca Bertero

E-Mail Website
Guest Editor
Pathology Unit, Department of Medical Sciences, University of Turin and “Città della Salute e della Scienza” University Hospital, Via Santena 7, 10126 Torino, Italy
Interests: pathology; neuropathology; molecular pathology; glioma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma remains the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. This Special Issue in Genes on “The Genomics of Glioblastoma” will refine the understanding of tumour heterogeneity and microenvironment, providing new approaches to the diagnosis and treatment of glioblastoma. We especially welcome original translational research studies (in vivo, in vitro) highlighting new findings in the above areas, and short communications of preliminary but significant experimental results. In addition, experts in the field will review the current diagnostic, therapeutic and experimental models in glioblastoma. Finally, manuscripts that address the key challenges in paediatric glioblastoma will be of interest.

Dr. Cristian Scatena
Dr. Francesco Pasqualetti
Dr. Luca Bertero
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioblastoma
  • genomics
  • tumour heterogeneity
  • tumour microenvironment

Published Papers (4 papers)

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Research

15 pages, 4375 KiB  
Article
The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw
by Lorenzo Innocenti, Valerio Ortenzi, Rosa Scarpitta, Nicola Montemurro, Francesco Pasqualetti, Roberta Asseri, Stefano Lazzi, Anna Szumera-Cieckiewicz, Katia De Ieso, Paolo Perrini, Antonio Giuseppe Naccarato, Cristian Scatena and Giuseppe Nicolò Fanelli
Genes 2023, 14(2), 501; https://doi.org/10.3390/genes14020501 - 15 Feb 2023
Cited by 5 | Viewed by 1372
Abstract
Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series [...] Read more.
Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (p < 0.0001 and p = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (rs = 0.417—p = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1–3.1, p = 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18–0.79, p = 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22–0.77, p = 0.006). Adjuvant treatment, methylguanine methyltransferase (MGMT) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM. Full article
(This article belongs to the Special Issue The Genomics of Glioblastoma)
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10 pages, 535 KiB  
Article
Prognostic Analysis of the IDH1 G105G (rs11554137) SNP in IDH-Wildtype Glioblastoma
by Ayoub Saaid, Matteo Monticelli, Alessia Andrea Ricci, Giulia Orlando, Cristina Botta, Pietro Zeppa, Andrea Bianconi, Simona Osella-Abate, Francesco Bruno, Alessia Pellerino, Roberta Rudà, Paola Cassoni, Diego Garbossa, Fabio Cofano and Luca Bertero
Genes 2022, 13(8), 1439; https://doi.org/10.3390/genes13081439 - 12 Aug 2022
Cited by 6 | Viewed by 1374
Abstract
The G105G SNP (rs11554137) in the IDH1 gene is observed in about 10–15% of patients with a diffuse glioma. Data regarding its impact on gliomas are poor and partially conflicting, possibly due to the evolving classification of CNS tumors. The aim of this [...] Read more.
The G105G SNP (rs11554137) in the IDH1 gene is observed in about 10–15% of patients with a diffuse glioma. Data regarding its impact on gliomas are poor and partially conflicting, possibly due to the evolving classification of CNS tumors. The aim of this study was to investigate the G105G SNP prognostic significance in a homogenous cohort of IDH-wildtype glioblastomas, in agreement with the 2021 WHO classification. The study analyzed 211 patients by collecting several clinico-pathological and molecular characteristics, including the age, lesion localization, number of involved lobes, type of surgical treatment, disease outcome and MGMT promoter methylation status. PFS and DSS curves were plotted according to the Kaplan–Meier method and statistical analyses were performed using parametric and non-parametric tests. A total of 32 patients out of 211 (15.2%) were found to be G105G SNP carriers. No significant impact of the IDH1 G105G SNP on patients’ outcomes was observed in terms of PFS and DSS, while MGMT promoter methylation and gross total resection resulted as key prognostic factors in our cohort as expected. No prognostic impact of the IDH1 G105G SNP was detected in this strict cohort of IDH-wildtype glioblastomas. Analysis of larger cohorts is warranted to address the sample size limitations. Full article
(This article belongs to the Special Issue The Genomics of Glioblastoma)
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9 pages, 771 KiB  
Article
Old and New Systemic Immune-Inflammation Indexes Are Associated with Overall Survival of Glioblastoma Patients Treated with Radio-Chemotherapy
by Francesco Pasqualetti, Celeste Giampietro, Nicola Montemurro, Noemi Giannini, Giovanni Gadducci, Paola Orlandi, Eleonora Natali, Paolo Chiarugi, Alessandra Gonnelli, Martina Cantarella, Cristian Scatena, Giuseppe Nicolò Fanelli, Antonio Giuseppe Naccarato, Paolo Perrini, Gaetano Liberti, Riccardo Morganti, Maria Franzini, Aldo Paolicchi, Giovanni Pellegrini, Guido Bocci and Fabiola Paiaradd Show full author list remove Hide full author list
Genes 2022, 13(6), 1054; https://doi.org/10.3390/genes13061054 - 13 Jun 2022
Cited by 16 | Viewed by 1889
Abstract
Background. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods. We tested 12 different SI using blood tests from patients with isocitrate [...] Read more.
Background. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods. We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results. A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26–84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions. This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L. Full article
(This article belongs to the Special Issue The Genomics of Glioblastoma)
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15 pages, 899 KiB  
Article
Pediatric High Grade Glioma Classification Criteria and Molecular Features of a Case Series
by Anna Maria Buccoliero, Laura Giunti, Selene Moscardi, Francesca Castiglione, Aldesia Provenzano, Iacopo Sardi, Mirko Scagnet, Lorenzo Genitori and Chiara Caporalini
Genes 2022, 13(4), 624; https://doi.org/10.3390/genes13040624 - 31 Mar 2022
Cited by 12 | Viewed by 4802
Abstract
Pediatric high-grade gliomas (pHGGs) encompass a heterogeneous group of tumors. Three main molecular types (H3.3 mutant, IDH mutant, and H3.3/IDH wild-type) and a number of subtypes have been identified. We provide an overview of pHGGs and present a mono-institutional series. We studied [...] Read more.
Pediatric high-grade gliomas (pHGGs) encompass a heterogeneous group of tumors. Three main molecular types (H3.3 mutant, IDH mutant, and H3.3/IDH wild-type) and a number of subtypes have been identified. We provide an overview of pHGGs and present a mono-institutional series. We studied eleven non-related pHGG samples through a combined approach of routine diagnostic tools and a gene panel. TP53 and H3F3A were the most mutated genes (six patients each, 54%). The third most mutated gene was EGFR (three patients, 27%), followed by PDGFRA and PTEN (two patients each, 18%). Variants in the EZHIP, MSH2, IDH1, IDH2, TERT, HRAS, NF1, BRAF, ATRX, and PIK3CA genes were relatively infrequent (one patient each, 9%). In one case, gene panel analysis documented the presence of a pathogenic IDH2 variant (c.419G>A, p.Arg140Gln) never described in gliomas. More than one-third of patients carry a variant in a gene associated with tumor-predisposing syndromes. The absence of constitutional DNA did not allow us to identify their constitutional origin. Full article
(This article belongs to the Special Issue The Genomics of Glioblastoma)
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