Papers by Delphine Poncet
International Journal of Molecular Sciences, Oct 8, 2019
Senescence is defined as a stress-induced durable cell cycle arrest. We herein revisit the origin... more Senescence is defined as a stress-induced durable cell cycle arrest. We herein revisit the origin of two of these stresses, namely mitochondrial metabolic compromise, associated with reactive oxygen species (ROS) production, and replicative senescence, activated by extreme telomere shortening. We discuss how replication stress-induced DNA damage of telomeric DNA (telDNA) and mitochondrial DNA (mtDNA) can be considered a common origin of senescence in vitro, with consequences on ageing in vivo. Unexpectedly, mtDNA and telDNA share common features indicative of a high degree of replicative stress, such as G-quadruplexes, D-loops, RNA:DNA heteroduplexes, epigenetic marks, or supercoiling. To avoid these stresses, both compartments use similar enzymatic strategies involving, for instance, endonucleases, topoisomerases, helicases, or primases. Surprisingly, many of these replication helpers are active at both telDNA and mtDNA (e.g., RNAse H1, FEN1, DNA2, RecQ helicases, Top2α, Top2β, TOP3A, DNMT1/3a/3b, SIRT1). In addition, specialized telomeric proteins, such as TERT (telomerase reverse transcriptase) and TERC (telomerase RNA component), or TIN2 (shelterin complex), shuttle from telomeres to mitochondria, and, by doing so, modulate mitochondrial metabolism and the production of ROS, in a feedback manner. Hence, mitochondria and telomeres use common weapons and cooperate to resist/prevent replication stresses, otherwise producing common consequences, namely senescence and ageing.
Molecular Diagnosis & Therapy, May 13, 2019
Background and objective Genomic duplications and fusion involving BRAF and KIAA1549 that create ... more Background and objective Genomic duplications and fusion involving BRAF and KIAA1549 that create fusion proteins with constitutive B-RAF kinase activity are a hallmark of pilocytic astrocytomas (PAs). The detection of KIAA1549-BRAF fusion transcripts is of paramount importance to classify these tumors and to identify patients who could benefit from BRAF inhibitors. In a clinical setting, the available material for molecular analysis from these pediatric tumors is often limited to formalin-fixed paraffin-embedded (FFPE) tissue. The aim of the present study was to develop a new method to detect the three most frequent KIAA1549-BRAF fusion transcripts, 15-9, 16-11, and 16-9, where numbers refer to the exons fused together, using a FFPE-compatible multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR). Methods We compared performance of the assay to a reference singleplex method on a collection of 46 FFPE PAs. Results The results showed that both methods are comparable. The multiplex method had an overall 97% sensitivity and 100% specificity compared to the singleplex method, and agreement between the two techniques was almost perfect (Cohen's kappa: 0.97). There was no evidence of a significant difference between the qRT-PCR efficiencies of the multiplex technique and of the singleplex assay for all fusion transcripts and for GAPDH, the latter used as a reference gene. The multiplex method consumed four times less complementary DNA (cDNA), cost less, and required half the hands-on technical time. Conclusion The results show that it could be beneficial to implement the multiplex method in a clinical setting, where samples presenting low quantity of degraded RNA are not unusual.
Neuro-oncology, Sep 1, 2018
NEURO-ONCOLOGY • SEPTEMBER 2018 gery in 18 cases (23.1%), radiotherapy in 10 cases (10.4%), and p... more NEURO-ONCOLOGY • SEPTEMBER 2018 gery in 18 cases (23.1%), radiotherapy in 10 cases (10.4%), and palliative care in 13 cases (16.7%)-we miss information about 4 patients. Median OS was 45.3 months (1.0-225.6). Factors positively associated with PFS and OS in univariate analysis were younger age, absence of contrast enhancement, and gross total resection. Age and extent of surgery retained a statistically significant importance in multivariate analysis. CONCLUSION: WHO grade II IDH-wild type gliomas have a worse outcome as compared with IDH-mutant tumours. This is the first study that details clinical and radiological presentation of this rare subgroup of tumours and suggests that gross total resection is critical in improving survival.
Bulletin Du Cancer, Jun 1, 2014
Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorect... more Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorectal cancer. Its anticancer activity results from its bioactivation into SN-38 metabolite, which is cleared through glucuronidation by the hepatic enzyme uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). In the general population, there is wide inter-subject variability in UGT1A1 enzyme activity related to UGT1A1 gene polymorphisms. The French joint workgroup coming from the National Pharmacogenetic Network (RNPGx) and the Group of Clinical Oncologic Pharmacology (GPCO) herein presents an updated review dealing with efficacy and toxicity clinical studies related to UGT1A1 genetic variants. From a critical analysis of this review it clearly emerges that, for doses higher than 180 mg/m(2), hematologic and digestive irinotecan-induced toxicities could be prevented in daily clinical practice by generalizing the use of a simple pharmacogenetic test before starting treatment. The clinical relevance of this test is also discussed in terms of treatment efficacy improvement, with the possibility of increasing the irinotecan dose in patients not bearing the deleterious allele. This test involves using a blood sample to analyze the promoter region of the UGT1A1 gene (UGT1A1*28 allele). Best execution practices, laboratory costs, as well as results interpretation are described with the aim of facilitating the implementation of this analysis in clinical routine. The existence of a French laboratories network performing this test in clinical routine makes it possible to generalize UGT1A1 deficiency screening, so as to guarantee equal access to safe treatment and optimized irinorecan-based therapy for the many patients receiving irinotecan-based therapy in advanced colorectal cancer.
Blood, Aug 4, 2011
Cells of B-cell chronic lymphocytic leukemia (B-CLL) are characterized by short telomeres despite... more Cells of B-cell chronic lymphocytic leukemia (B-CLL) are characterized by short telomeres despite a low proliferative index. Because telomere length has been reported to be a valuable prognosis criteria, there is a great interest in a deep understanding of the origin and consequences of telomere dysfunction in this pathology. Cases of chromosome fusion involving extremely short telomeres have been reported at advanced stage. In the present study, we address the question of the existence of early telomere dysfunction during the B-CLL time course. In a series restricted to 23 newly diagnosed Binet stage A CLL patients compared with 12 healthy donors, we found a significant increase in recruitment of DNA-damage factors to telomeres showing telomere dysfunction in the early stage of the disease. Remarkably, the presence of dysfunctional telomeres did not correlate with telomere shortening or chromatin marks deregulation but with a downregulation of 2 shelterin genes: ACD (coding for TPP1; P ؍ .0464) and TINF2 (coding for TIN2; P ؍ .0177). We propose that telomeric deprotection in the early step of CLL is not merely the consequence of telomere shortening but also of shelterin alteration.
Fundamental & Clinical Pharmacology, May 4, 2015
Irinotecan is a major drug in the treatment of advanced colorectal cancer. Its active form is the... more Irinotecan is a major drug in the treatment of advanced colorectal cancer. Its active form is the SN38 metabolite, which is cleared by the biliary route after glucuronidation by uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). UGT1A1 activity exhibits a wide inter-subject variability, in part related to UGT1A1 gene polymorphisms. The present review on the impact of the deficient UGT1A1*28 variant on irinotecan efficacy and toxicity was produced by a French joint workgroup comprising the Group of Clinical Onco-pharmacology (GPCO-Unicancer) and the National Pharmacogenetics Network (RNPGx). It clearly emerges that for irinotecan doses at least equal to 180 mg/m(2) , patients homozygous for the UGT1A1*28 allele are at increased risk of developing haematological and/or digestive toxicities. Irinotecan dose reduction is thus recommended in homozygous *28/*28 patients. In addition, this personalized medicine strategy aims to secure high-dose irinotecan administration (≥240 mg/m(2) ) that have proven to be safe in homozygous *1/*1 patients only. The clinical relevance of this test is discussed in terms of treatment efficacy improvement, since increasing the irinotecan dose appears to be safe in patients not bearing a deficient allele. Best execution practices, cost-effectiveness, as well as result interpretation are discussed with the aim of facilitating the implementation of this analysis in clinical practice. The existence of networks of laboratories performing this test in routine hospital treatment, as in France, offers the prospect of widespread screening, thus guaranteeing equal access to safe treatment and optimized therapy for patients receiving irinotecan-based therapy in advanced colorectal cancer. This article is protected by copyright. All rights reserved.
Oncogene, Dec 12, 2002
One of the mechanisms by which chemotherapeutics destroy cancer cells is by inducing apoptosis. A... more One of the mechanisms by which chemotherapeutics destroy cancer cells is by inducing apoptosis. Apoptosis can be activated through several different signalling pathways, but these all appear to converge at a single event-mitochondrial membrane permeabilization (MMP). This 'point-of-no-return' in the cell death program is a complex process that is regulated by the composition of the mitochondrial membrane and premitochondrial signal-transduction events. MMP is subject to a complex regulation, and local alterations in the composition of mitochondrial membranes, as well as alterations in pre-mitochondrial signal-transducing events, can determine chemotherapy resistance in cancer cells. Detecting MMP might thus be useful for detecting chemotherapy responses in vivo. Several cytotoxic drugs induce MMP by a direct action on mitochondria. This type of agents can enforce death in cells in which upstream signals normally leading to apoptosis have been disabled. Cytotoxic components acting on mitochondria can specifically target proteins from the Bcl-2 family, the peripheral benzodiazepin receptor, or the adenine nucleotide translocase, and/or act by virtue of their physicochemical properties as steroid analogues, cationic ampholytes, redox-active compounds or photosensitizers. Some compounds acting on mitochondria can overcome the cytoprotective effect of Bcl-2-like proteins. Several agents which are already used in anti-cancer chemotherapy can induce MMP, and new drugs specifically designed to target mitochondria are being developed.
Neurosurgery, Nov 8, 2018
BACKGROUND Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated wi... more BACKGROUND Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis. OBJECTIVE To analyze the radiological presentation and natural history of adult IDH-wildtype astrocytomas with TERTp. METHODS We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas. RESULTS Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged >50 yr (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥8 mm/yr but 7 cases displayed a slow growth (VDE <8 mm/yr) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 mo. CONCLUSION IDH-wildtype TERTp-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged >50 yr. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.
Journal of Neuropathology and Experimental Neurology, Aug 8, 2020
Pleomorphic xanthoastrocytoma (PXA) is classified as an astrocytic glioma occurring most often in... more Pleomorphic xanthoastrocytoma (PXA) is classified as an astrocytic glioma occurring most often in children or young adults. Molecular alterations in PXA are not fully known, especially those associated with tumor progression. We describe a patient with several relapses of a PXA. The tumor showed an acquired ATRX loss through tumor evolution. We tested alternative lengthening of telomeres (ALT) with the C-circle test. While the test was negative in the first tumor, a high circle activity was detected in the last relapse, suggesting an acquired ALT phenotype. Our data not only confirm previous findings of the possible occurrence of ATRX mutations in PXA but also suggest that this alteration is linked to PXA progression. In small biopsies, tumors with ATRX loss, without IDH or histone mutation, pathologists should consider the diagnosis of PXA, especially if associated with BRAF V600E mutation, CDKN2A deletion, and ALT.
American Journal of Surgical Pathology
Adult tumors diagnosed as cerebellar glioblastoma (cGBM) are rare and their optimal classificatio... more Adult tumors diagnosed as cerebellar glioblastoma (cGBM) are rare and their optimal classification remains to be determined. The aim of this study was to identify subgroups of cGBM based on targeted molecular analysis. cGBM diagnosed between 2003 and 2017 were identified from the French Brain Tumor Database and reviewed according to the WHO 2021 classification. The following molecular alterations were studied: IDH1/2, H3F3A, FGFR1, BRAF, TERT promoter mutations, EGFR amplification, MGMT promoter methylation, and alternative lengthening of telomere status. DNA methylation profile was assessed in a subset of cases. Eighty-three cGBM were included and could be classified into 6 mutually exclusive subgroups associated with median age at diagnosis (MA) and prognosis: TERT-mutant and/or EGFR-amplified tumors (n=22, 26.5%, MA=62 y, median overall survival [OS]=4 mo), H3K27M-mutant tumors (n=15, 18.1%, MA=48 y, median OS=8 mo), mitogen-activated protein kinases (MAPK) pathway–activated tumo...
Journal of Neuro-Oncology
Molecular glioblastomas (i.e. without the histological but with the molecular characteristics of ... more Molecular glioblastomas (i.e. without the histological but with the molecular characteristics of IDH-wild-type glioblastoma) frequently lack contrast enhancement, which can wrongly lead to suspect a lower-grade glioma. Herein, we aimed to assess the diagnostic value of gyriform infiltration as an imaging marker for molecular glioblastomas. Two independent investigators reviewed the MRI scans from patients with newly diagnosed gliomas for the presence of a gyriform infiltration defined as an elective cortical hypersignal on MRI FLAIR sequence. Diagnostic test performance of this sign for the diagnosis of molecular glioblastoma were calculated. A total of 426 patients were included, corresponding to 31 molecular glioblastoma, 294 IDH-wild-type glioblastoma, 50 IDH-mutant astrocytoma, and 51 IDH-mutant 1p19q-codeleted oligodendroglioma. A gyriform infiltration was observed in 16/31 (52%) molecular glioblastoma, 40/294 (14%) IDH-wild-type glioblastoma, and none of the IDH-mutant glioma. All the 56 gyriform-infiltration-positive tumors were IDH-wild-type and all but two had a TERT promoter mutation. The inter-rater agreement was good (κ = 0.69, p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the presence of a gyriform infiltration for the diagnosis of molecular glioblastoma were 52%, 90%, 29%, 96%, respectively. The median overall survival was better for gyriform-infiltration-negative patients compared to gyriform-infiltration-positive patients in the whole series and in patients with non-enhancing lesions (n = 95) (25.6 vs 16.9 months, p = 0.005 and 20.2 months vs not reached, p < 0.001). Gyriform infiltration is a specific imaging marker of molecular glioblastomas that can help distinguishing these tumors from IDH-mutant lower-grade gliomas.
Annals of Oncology, 2021
BACKGROUND In glioma, TERT promoter mutation and loss of ATRX (ATRX loss) are associated with rea... more BACKGROUND In glioma, TERT promoter mutation and loss of ATRX (ATRX loss) are associated with reactivation of telomerase or alternative lengthening of telomeres (ALT), respectively, i.e. the two telomere maintenance mechanisms (TMM). Strangely, 25% of gliomas have been reported to display neither or both of these alterations. MATERIALS AND METHODS The C-circle (CC) assay was adapted to tumor (formalin-fixed paraffin-embedded and frozen) and blood samples to investigate the TMM. RESULTS We constructed a CC-based algorithm able to identify the TMM and reported a sensitivity of 100% and a specificity of 97.3% (n = 284 gliomas). By combining the TMM, the mutational status of the isocitrate dehydrogenase 1/2 (IDH) gene (IDHmt), and the histological grading, we propose a new classification tool: TeloDIAG. This classification defined five subtypes: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low-grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma (GBM), respectively; the last class gathers ALT+ IDHwt gliomas that tend to be related to longer survival (21.2 months) than tGBM (16.5 months). The TeloDIAG was 99% concordant with the World Health Organization classification (n = 312), and further modified the classification of 55 of 144 (38%) gliomas with atypical molecular characteristics. As an example, 14 of 69 (20%) of TERTwt, ATRXwt, and IDHwt GBM were actually tAIV. Outstandingly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 97% (n = 206 gliomas and 30 healthy donors). CONCLUSION The TeloDIAG is a new, simple, and effective tool helping in glioma diagnosis and a promising option for liquid biopsy.
Neuro-Oncology, 2021
BACKGROUND Diffuse astrocytic gliomas, IDH wildtype, with molecular features of glioblastoma (mol... more BACKGROUND Diffuse astrocytic gliomas, IDH wildtype, with molecular features of glioblastoma (molecular glioblastomas) are associated with a poor prognosis. We previously found that these tumors frequently display gyriform infiltration, defined as areas of elective cortical hypersignal on MRI FLAIR sequence. The objective of the present study was to assess the diagnostic value of gyriform infiltration as an imaging marker for these tumors. MATERIAL AND METHODS MRI scans from 430 patients with newly diagnosed glioma (molecular glioblastoma n = 31, IDH wildtype glioblastoma n = 298, IDH-mutant astrocytoma n = 50, IDH-mutant and 1p19q codeleted oligodendroglioma n= 51) were evaluated for the presence of a gyriform infiltration by 2 independent reviewers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the performance of the presence of a gyriform infiltration for identifying molecular glioblastoma. RESULTS A gyrif...
Neuro-Oncology, 2021
BACKGROUND Adult cerebellar glioblastomas (cGBM) are very rare and recent studies have shown that... more BACKGROUND Adult cerebellar glioblastomas (cGBM) are very rare and recent studies have shown that they constitute a heterogeneous group of gliomas. The aim of the present study was to characterize the prevalence and prognostic significance of major driver molecular alterations in a large series of cGBM. MATERIAL AND METHODS Adults with histologically proven cGBM diagnosed between 2003 and 2017 were identified from the French brain tumor database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie. Tumors were reviewed and reclassified according to WHO 2016. Targeted sequencing was performed, including determination of H3F3A, TERTp, IDH1/2, FGFR1, BRAF and EGFR status. RESULTS A total of 83 adult patients (median age 57 years) with cGBM (hemispheric n= 47, vermian n=14 or both n=22) were identified. Median overall survival was 10 months. Main molecular alterations observed were TERT promoter, H3F3A K27M, hotspot FGFR1 (N546 and K656), BRAF mutations, EGFR ampli...
Neurosurgery, 2020
BACKGROUND Biopsies in patients with a suspected glioma are occasionally nondiagnostic. OBJECTIVE... more BACKGROUND Biopsies in patients with a suspected glioma are occasionally nondiagnostic. OBJECTIVE To explore the utility of molecular testing in this setting by determining whether IDH1 and TERT promoter (pTERT) mutations could be detected in nondiagnostic biopsies from glioma patients. METHODS Using SNaPshot polymerase chain reaction, we retrospectively assessed IDH1 and pTERT mutation status in nondiagnostic biopsies from 28 glioma patients. RESULTS The nondiagnostic biopsy (needle biopsy n = 25, open or endoscopic biopsy n = 3) consisted of slight glial cell hypercellularity, hemorrhage, and/or necrosis. After another biopsy (n = 23) or a subsequent surgical resection (n = 5) the diagnosis was an IDH1-wildtype (WT) pTERT-mutant glioma (glioblastoma n = 16, astrocytoma n = 4), an IDH1-mutant pTERT-mutant oligodendroglioma (n = 1), an IDH1-mutant pTERT-WT astrocytoma (n = 1), and an IDH1-WT pTERT-WT glioblastoma (n = 6). An IDH1 mutation was identified in the nondiagnostic biopsies...
Neuro-Oncology, 2019
BACKGROUND H3 G34-mutant high-grade gliomas occur primarily in children but can also be encounter... more BACKGROUND H3 G34-mutant high-grade gliomas occur primarily in children but can also be encountered in adults. The aim of the present study was to describe the characteristics of H3 G34-mutant high-grade gliomas in adults. MATERIAL AND METHODS We analysed the characteristics of 17 adult H3 G34-mutant high-grade gliomas and compared them with those of adult grade IV gliomas with H3 K27M mutation (n=21), IDH mutation (n=42) and TERT promoter (pTERT) mutation (n=88). RESULTS Median age at diagnosis in H3 G34-mutant gliomas was 25 years (range: 19–33 y). All tumors had a hemispheric location. The radiological presentation was suggestive of a high-grade glioma in 6 patients but in 10 patients it initially suggested another diagnosis due to absent or faint contrast enhancement (n=9) or the presence of an initial intratumoral haemorrhage (n=1). In non- or faint contrast-enhancing cases, diffusion-weighted imaging (DWI) was more helpful to suspect an aggressive tumor than MR spectroscopy an...
Medical project adenoid cystic carcinomas, melanomas mucosal chordomas, chondrosarcomas of the ax... more Medical project adenoid cystic carcinomas, melanomas mucosal chordomas, chondrosarcomas of the axial skeleton, desmoid tumors, pelvic recurrences of rectal cancer and aggressive forms of meningiomas. Keeping up to date and scientific veille monitoring Throughout the acquisition process, data are updated if necessary. In 2012 we updated the data upon sarcomas and brain tumors in children. This topic resulted in a manuscript being finalized.
Cancer Letters, 2015
This study aimed to examine the cellular and molecular long-term responses of glioblastomas to ra... more This study aimed to examine the cellular and molecular long-term responses of glioblastomas to radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Eleven human glioblastoma cell lines, displaying gradual radiosensitivity, were irradiated with photons or carbon ions. Independently of p53 or O(6)-methylguanine-DNA methyltransferase(1) status, all cell lines responded to irradiation by a G2/M phase arrest followed by the appearance of mitotic catastrophe, which was concluded by a ceramide-dependent-apoptotic cell death. Statistical analysis demonstrated that: (i) the SF2(2) and the D10(3) values for photon are correlated with that obtained in response to carbon ions; (ii) regardless of the p53, MGMT status, and radiosensitivity, the release of ceramide is associated with the induction of late apoptosis; and (iii) the appearance of polyploid cells after photon irradiation could predict the Relative Biological Efficiency(4) to carbon ions. This large collection of data should increase our knowledge in glioblastoma radiobiology in order to better understand, and to later individualize, appropriate radiotherapy treatment for patients who are good candidates.
Neuro-Oncology, 2021
BACKGROUND The integration of molecular markers into the WHO 2016 classification has clarified th... more BACKGROUND The integration of molecular markers into the WHO 2016 classification has clarified the complex diagnosis of gliomas. Among these biomarkers, the TERT promoter mutation and the loss of ATRX (ATRX loss) are mutually exclusive alterations associated with re-activation of telomerase or alternative lengthening of telomeres (ALT), respectively. Strangely, 25% of gliomas display neither or both these alterations, a situation referred to as abnormal telomere maintenance mechanism (aTMM). MATERIAL AND METHODS To investigate the TMM actually involved in gliomas, the C-circle (CC) assay was adapted to tumor (FFPE and frozen) samples. RESULTS We constructed a CC-based algorithm able to identify the TMM of 284 gliomas with either TERT or ATRX alteration, with a sensitivity of 100% and a specificity of 97.3%, and succeeded in deciphering the TMM involved in 122 aTMM gliomas. Additionally, the combination of the TMM, the mutational status of the Isocitrate dehydrogenase 1/2 (IDH) gene,...
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Papers by Delphine Poncet