Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide

Gomes, Isabella; Moreno, Daniel Antunes; Reis, Mariana Bisarro dos; Silva, Luciane Sussuchi da; Leal, Letícia Ferro; Gonçalves, Gisele Melo; Pereira, Caio Augusto; Oliveira, Marco Antônio de; Matsushita, Marcus de Medeiros; Reis, Rui Manuel

doi:10.1007/s11060-020-03675-6

Cited by 16 publications

(16 citation statements)

References 42 publications

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“…Nucleic Acid Isolation DNA and RNA isolation was performed from FFPE tumor tissue, sectioned on slides with a thickness of 10 μm (minimum of 60% tumor area) using the QIAamp DNA Micro Kit (QIAGEN, Hilden, Germany) and RNeasy FFPE Mini Kit (QIAGEN). Measurement of RNA and DNA quantity was done with the Qubit Fluorometric Quantification system (Life Technologies) as previously reported [20]. For fusion analysis, RNA quantity was assessed using 4150 TapeStation (Agilent Technologies) following the manufacturer's instructions.…”

Section: Molecular Profilingmentioning

confidence: 99%

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib

et al. 2022

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Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a TPR-NTRK1 gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring NTRK1 rearrangement treated with larotrectinib.

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Section: Molecular Profilingmentioning

confidence: 99%

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib

et al. 2022

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“…These patients were previously characterized molecularly for IDH1 mutation status, ATRX expression, TERT promoter mutations, and MGMT methylation. 9 The clinicopathological and molecular features are summarized in Supplemental Table 1 . The 13 grade 4 astrocytomas, IDH mutant included in the present study, showed microvascular proliferation, necrosis, and IDH1 R132H mutation.…”

Section: Methodsmentioning

confidence: 99%

“… 8 Importantly, some prognostic biomarkers are reported, the O6-methylguanine-DNA methyltransferase ( MGMT ) methylation status is one of the most widely used biomarkers. 9 …”

Section: Introductionmentioning

confidence: 99%

Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients’ survival

et al. 2022

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Introduction: Glioblastoma (GBM), isocitrate dehydrogenase ( IDH) wild-type ( IDHwt), and grade 4 astrocytomas, IDH mutant ( IDHmut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDHwt GBM and IDHmut tumors and identify prognostic biomarkers and a gene signature associated with patient survival. Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDHwt GBM compared to IDHmut tumors. Regarding IDHwt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDHwt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients’ prognosis.

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“…Expression profile of NTERA-2R and NTERA-2P was performed using nCounter Vantage 3D DNA Damage and Repair panel (Nanostring, USA) as previously reported [36], to evaluate features related to CDDP-resistance. This panel includes 180 genes involved in major DNA damage repair pathways, including base excision repair, nucleotide excision repair, mismatch repair, TLS, and other repair processes (available at: http://nanostring.com).…”

Section: Expression Profile Of Cddp-resistance In Vitro Modelmentioning

confidence: 99%

Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors

Lengert¹,

Pereira²,

Cabral³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Testicular germ cell tumors (TGCTs), a group of heterogeneous neoplasms, are the most frequent tumors of teenagers and young men, with the incidence rising worldwide. High cure rates can be achieved through cisplatin (CDDP)-based treatment, but approximately 10% of patients present refractory disease and virtually no treatment alternatives. Here, we explored new strategies to treat CDDP-resistant. Methods: In vitro TGCT CDDP-resistance model was established and differential mRNA expression profiles were evaluated using NanoString technology. Then, TGCT cell lines were treated with four potential drugs (PCNA-I1, ML323, T2AA, and MG-132) to overcome CDDP-resistance. Results: We found several differentially expressed genes related to DNA repair and cell cycle regulation on CDDP-resistant cell line (NTERA-2R) compared to parental cell line (NTERA-2P), and the proteasome inhibitor MG-132 demonstrated cytotoxic activity in all cell lines evaluated, even at a nanomolar range. MG-132 also enhanced cell lines' sensitivity to CDDP, increasing apoptosis in both NTERA-2P and NTERA-2R. Conclusions: MG-132 emerges as a potential new drug to treat CDDP-resistant TGCT. Targeted therapy based on molecular mechanism insights may contribute to overcome acquired chemotherapy CDDP-resistance.

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Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide

Cited by 16 publications

References 42 publications

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with <b><i>TPR</i></b>-<b><i>NTRK1</i></b> Fusion Treated with Larotrectinib

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with <b><i>TPR</i></b>-<b><i>NTRK1</i></b> Fusion Treated with Larotrectinib

Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients’ survival

Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors

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