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Epigenetic gene alterations in metastatic solid tumours: results from the prospective precision medicine MOSCATO and MATCH-R trials.
Martin-Romano, Patricia; Colmet-Daage, Leo; Morel, Daphne; Baldini, Capucine; Verlingue, Loic; Bahleda, Rastilav; Gazzah, Anas; Champiat, Stephan; Varga, Andree; Michot, Jean Marie; Ngo-Camus, Maud; Nicotra, Claudio; Marabelle, Aurelien; Soria, Jean Charles; Rouleau, Etienne; Lacroix, Ludovic; Hollebecque, Antoine; Massard, Christophe; Postel-Vinay, Sophie.
Afiliación
  • Martin-Romano P; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Colmet-Daage L; Inserm Unit U981, ATIP-Avenir Team, Villejuif, France.
  • Morel D; Inserm Unit U981, ATIP-Avenir Team, Villejuif, France.
  • Baldini C; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Verlingue L; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Bahleda R; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Gazzah A; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Champiat S; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Varga A; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Michot JM; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Ngo-Camus M; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Nicotra C; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Marabelle A; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Soria JC; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Inserm Unit U981, ATIP-Avenir Team, Villejuif, France.
  • Rouleau E; Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France.
  • Lacroix L; Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France.
  • Hollebecque A; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • Massard C; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Inserm Unit U981, ATIP-Avenir Team, Villejuif, France.
  • Postel-Vinay S; Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Inserm Unit U981, ATIP-Avenir Team, Villejuif, France. Electronic address: Sophie.postel-vinay@gustaveroussy.fr.
Eur J Cancer ; 173: 133-145, 2022 09.
Article en En | MEDLINE | ID: mdl-35872509
INTRODUCTION: Although the role of epigenetic alterations in oncogenesis has been well studied, their prevalence in metastatic solid tumours is still poorly described. We therefore aimed at: (i) describing the presence of epigenetic gene alterations (EGA) - defined by an alteration in a gene encoding an epigenetic regulator; and (ii) evaluating their relationship with clinical characteristics and outcome in patients (pts) included in prospective molecular profiling trials. MATERIALS AND METHODS: On-purpose tumour biopsies from pts with metastatic solid tumours enrolled in the Gustave Roussy-sponsored MOSCATO (NCT01566019) and MATCHR (NCT02517892) trials were molecularly profiled using whole exome sequencing (WES). Alterations in 176 epigenetic genes were assessed and classified as pathogenic variants (PV) or non-pathogenic variants by a molecular tumour board. Clinical characteristics and outcome were collected. RESULTS: Between Dec 2011 and Oct 2016, WES was successfully performed in 292 pts presenting various solid tumours. We found 496 epigenetic gene alterations in 134 patients (49%), including 237 pathogenic variants in 86 patients; 63 tumour samples (47%) presented ≥3 EGAs. The median number of previous treatment lines was 3 (1-10). The most frequently altered genes were KMT2D and KMT2C (16% each), ARID1A and SETD2 (10% each) and KMT2A (8%).; 31% of EGA co-occurred with a driver gene alteration (p < 0.001). Outcome was not correlated with the presence of EGA. CONCLUSIONS: Epigenetic alterations occur frequently in metastatic solid tumours. With the current development of epigenetic modifiers, they increasingly represent actionable targets. Such genes should now be systematically analysed in molecular profiling studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Medicina de Precisión / Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Eur J Cancer Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Medicina de Precisión / Neoplasias Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Eur J Cancer Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido