Sabrina Fritah

OS03.5.A FUNCTIONAL PRECISION MEDICINE SCREENING REVEALS PERSONALIZED THERAPEUTIC VULNERABILITIES IN HIGH-GRADE GLIOMA SUBTYPES

Luca Ermini, A Lipsa, Ann‐Christin Hau, Iryna Krokhmal et autres

Abstract BACKGROUND Precision medicine has transformed cancer treatment by tailoring therapies to the specific molecular aberrations of an individual patient’s tumor. The integration of high-resolution multi-omics with high-throughput functional profiling holds the potential to further refine patient stratification, advancing personalized medicine and …

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Integrative multi-omics combined with functional pharmacological profiling in patient-derived organoids identifies personalized therapeutic vulnerabilities of adult high-grade gliomas

Luca Ermini, Anuja Lipsa, Ann‐Christin Hau, Iryna Krokhmal et autres

ABSTRACT Background Precision medicine has transformed cancer treatment by tailoring therapies to specific molecular aberrations. Integrating high-resolution multi-omics with high-throughput functional profiling in patient-derived organoids of-fers a powerful strategy to further refine patient stratification. While (epi)genetic profiling has drastically improved the classification …

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P02.18.B INTEGRATIVE OMICS ANALYSIS OF IDH1 MUTANT GLIOMA PATIENTS REVEALS ALTERATIONS IN BUTYRATE METABOLISM

Sabrina Fritah, Andrés Cano-Galiano, Réka Tóth, Ann‐Christin Hau et autres

Abstract BACKGROUND Mutations in isocitrate dehydrogenase (IDH) 1 or 2 define glioma classification and determine the biology of these tumors. Although IDH is an essential enzyme in the cellular metabolism, powerful genome-wide analyses focus mostly at the genetic and epigenetic levels, while …

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Impact of IDH Mutations, the 1p/19q Co-Deletion and the G-CIMP Status on Alternative Splicing in Diffuse Gliomas

Lu Zhang, Sabrina Fritah, Petr V. Nazarov, Tony Kaoma et autres

By generating protein diversity, alternative splicing provides an important oncogenic pathway. Isocitrate dehydrogenase (IDH) 1 and 2 mutations and 1p/19q co-deletion have become crucial for the novel molecular classification of diffuse gliomas, which also incorporates DNA methylation profiling. In this study, we …

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Review of Current Human Genome-Scale Metabolic Models for Brain Cancer and Neurodegenerative Diseases

Ali Kishk, Maria Pires Pacheco, Tony Heurtaux, Lasse Sinkkonen et autres

Brain disorders represent 32% of the global disease burden, with 169 million Europeans affected. Constraint-based metabolic modelling and other approaches have been applied to predict new treatments for these and other diseases. Many recent studies focused on enhancing, among others, drug predictions …

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PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing

Egle Danileviciute, Ni Zeng, Christophe Capelle, Nicole Paczia et autres

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XAB2 promotes Ku eviction from single-ended DNA double-strand breaks independently of the ATM kinase

Abhishek Bharadwaj Sharma, Hélène Erasimus, Lia Pinto, Marie‐Christine Caron et autres

Replication-associated single-ended DNA double-strand breaks (seDSBs) are repaired predominantly through RAD51-mediated homologous recombination (HR). Removal of the non-homologous end-joining (NHEJ) factor Ku from resected seDSB ends is crucial for HR. The coordinated actions of MRE11-CtIP nuclease activities orchestrated by ATM define one …

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Chromosome Y pericentric heterochromatin is a primary target of HSF1 in male cells

Jessica Penin, Solenne Dufour, Virginie Faure, Sabrina Fritah et autres

The heat shock factor 1 (HSF1)-dependent transcriptional activation of human pericentric heterochromatin in heat-shocked cells is the most striking example of transcriptional activation of heterochromatin. Until now, pericentric heterochromatin of chromosome 9 has been identified as the primary target of HSF1, in …

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Temozolomide-Induced RNA Interactome Uncovers Novel LncRNA Regulatory Loops in Glioblastoma

Sabrina Fritah, Arnaud Muller, Wei Jiang, Ramkrishna Mitra et autres

Resistance to chemotherapy by temozolomide (TMZ) is a major cause of glioblastoma (GBM) recurrence. So far, attempts to characterize factors that contribute to TMZ sensitivity have largely focused on protein-coding genes, and failed to provide effective therapeutic targets. Long noncoding RNAs (lncRNAs) …

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XAB2 prevents abortive recombinational repair of replication-associated DNA double-strand breaks and its loss is synthetic lethal with RAD52 inhibition

Abhishek Bharadwaj Sharma, Hélène Erasimus, Lia Pinto, Marie‐Christine Caron et autres

ABSTRACT Unrepaired O 6 -methylguanine lesions induced by the alkylating chemotherapy agent temozolomide lead to replication-associated single-ended DNA double-strand breaks (seDSBs) that are repaired predominantly through RAD51-mediated homologous recombination (HR). Here, we show that loss of the pre-mRNA splicing and DNA repair …

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Dual blockade of STAT3 and EGFR: a key to unlock drug resistance in glioblastoma?

Sabrina Fritah, Simone P. Niclou

See the article by Fan and An et al in this issue, pp. 457–469. The lack of effective therapy against glioblastoma (GBM) is largely linked to tumor heterogeneity and high drug resistance. Primary resistance to chemotherapy stems from intrinsic properties of cancer …

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Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling

Mingzhi Han, Shuai Wang, Sabrina Fritah, Xu Wang et autres

Long non-coding RNAs play critical roles in tumour progression. Through analysis of publicly available genomic datasets, we found that MIR22HG, the host gene of microRNAs miR-22-3p and miR-22-5p, is ranked among the most dysregulated long non-coding RNAs in glioblastoma. The main purpose …

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