Targetable Alterations in Adult Patients With Soft-Tissue Sarcomas: Insights for Personalized Therapy
| dc.rights.license | open | en_US |
| dc.contributor.author | LUCCHESI, C. | |
| dc.contributor.author | KHALIFA, E. | |
| dc.contributor.author | LAIZET, Y. | |
| dc.contributor.author | SOUBEYRAN, I. | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | MATHOULIN-PELISSIER, Simone | |
| dc.contributor.author | CHOMIENNE, C. | |
| dc.contributor.author | ITALIANO, A. | |
| dc.date.accessioned | 2020-11-30T13:34:10Z | |
| dc.date.available | 2020-11-30T13:34:10Z | |
| dc.date.issued | 2018-10-01 | |
| dc.identifier.issn | 2374-2445 (Electronic) 2374-2437 (Linking) | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/21265 | |
| dc.description.abstractEn | Importance: Patients with advanced soft-tissue sarcomas (STS) have a median overall survival of less than 18 months. Identification of molecular abnormalities for which targeted therapies are available or can be developed is critical for improving patient outcomes. Objective: To characterize targetable genomic alterations (GAs) in patients with STS. Design, Setting, and Participants: This cross-sectional study of next-generation sequencing results from 584 patients with STS included in the AACR GENIE Database. Main Outcomes and Measures: Presence of targetable GAs in STS. Results: Of 584 patients included in the analysis, 294 (50.3%) were men and 290 (49.7%) were women, with a median age of 56 years (range, 18-89 years). There were 331 (57%) patients with complex genomics sarcomas, 144 (25%) with translocation-related sarcomas, and 112 (18%) with other sarcomas (inactivating mutation, simple amplicon). A total of 2697 alterations were identified in 451 genes (1154 substitutions, 765 gene amplifications, 364 short indels and splicing variants, 346 gene homozygous deletions, and 68 gene rearrangements) with a median of 4 (1-53) per case. In order of frequency, the 20 genes most often altered were: TP53, MDM2, CDK4, RB1, ATRX, CDKN2A, PTEN, NF1, CDKN2B, KMT2D, GLI1, ATM, TERT, PI3KCA, NOTCH1, MAP2K4, ERBB4, ARID1A, TSC2, and TNFAIP3. At least 1 targetable GA was found in 239 cases (41%) with a statistically significant higher number in other and complex genomics sarcomas than in translocation-related sarcomas (respectively other: n=89, 82%, complex: n = 131, 40%, translocation: n = 19, 13%; chi2 test, P < .001). Conclusions and Relevance: Up to 41% of STS harbored at least 1 clinically relevant GA with potential to influence and personalize therapy. Comprehensive genomic profiling can identify novel treatment paradigms to address the limited options and poor prognoses of patients with STS. | |
| dc.language.iso | EN | en_US |
| dc.subject.en | EPICENE | |
| dc.title.en | Targetable Alterations in Adult Patients With Soft-Tissue Sarcomas: Insights for Personalized Therapy | |
| dc.title.alternative | JAMA Oncol | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1001/jamaoncol.2018.0723 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
| dc.identifier.pubmed | 29801054 | en_US |
| bordeaux.journal | JAMA oncology | en_US |
| bordeaux.page | 1398-1404 | en_US |
| bordeaux.volume | 4 | en_US |
| bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
| bordeaux.issue | 10 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.team | EPICENE | en_US |
| bordeaux.team | EPICENE_BPH | |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-03193184 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-04-08T13:50:41Z | |
| hal.export | true | |
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