Your browser doesn't support javascript.
loading
Comprehensive clinicopathological and genomic profiling of gallbladder cancer reveals actionable targets in half of patients.
de Bitter, Tessa J J; de Reuver, Philip R; de Savornin Lohman, Elise A J; Kroeze, Leonie I; Vink-Börger, Marianne E; van Vliet, Shannon; Simmer, Femke; von Rhein, Daniel; Jansen, Erik A M; Verheij, Joanne; van Herpen, Carla M L; Nagtegaal, Iris D; Ligtenberg, Marjolijn J L; van der Post, Rachel S.
Afiliación
  • de Bitter TJJ; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands. Tessa.JJ.deBitter@radboudumc.nl.
  • de Reuver PR; Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Surgery, Nijmegen, The Netherlands.
  • de Savornin Lohman EAJ; Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Surgery, Nijmegen, The Netherlands.
  • Kroeze LI; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands.
  • Vink-Börger ME; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands.
  • van Vliet S; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands.
  • Simmer F; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands.
  • von Rhein D; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Human Genetics, Nijmegen, The Netherlands.
  • Jansen EAM; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Human Genetics, Nijmegen, The Netherlands.
  • Verheij J; Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands.
  • van Herpen CML; Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Medical Oncology, Nijmegen, The Netherlands.
  • Nagtegaal ID; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands.
  • Ligtenberg MJL; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Pathology, Nijmegen, The Netherlands.
  • van der Post RS; Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Human Genetics, Nijmegen, The Netherlands.
NPJ Precis Oncol ; 6(1): 83, 2022 Nov 05.
Article en En | MEDLINE | ID: mdl-36335173
ABSTRACT
Gallbladder cancer (GBC) is a rare, highly aggressive malignancy with a 5-year survival rate of 5-10% in advanced cases, highlighting the need for more effective therapies. The aim of this study was to identify potentially actionable therapeutic targets for GBC. Specimens and clinicopathological data of 642 GBC patients, diagnosed between 2000 and 2019 were collected using the Dutch Pathology Registry (PALGA) and the Netherlands Cancer Registry. All cases were histologically reviewed and a subset was subjected to a comprehensive next generation sequencing panel. We assessed mutations and gene amplifications in a panel of 54 actionable genes, tumor-mutational burden (TMB), and microsatellite instability (MSI). Additionally, the entire cohort was screened for HER2, PD-L1, pan-TRK, and p53 expression with immunohistochemistry. Histopathological subtypes comprised biliary-type adenocarcinoma (AC, 69.6%), intestinal-type AC (20.1%) and other subtypes (10.3%). The median total TMB was 5.5 mutations/Mb (range 0-161.1) and 17.7% of evaluable cases had a TMB of >10 mutations/Mb. MSI was observed in two cases. Apart from mutations in TP53 (64%), tumors were molecularly highly heterogeneous. Half of the tumors (50%) carried at least one molecular alteration that is targetable in other tumor types, including alterations in CDKN2A (6.0% biallelically inactivated), ERBB2 (9.3%) and PIK3CA (10%). Immunohistochemistry results correlated well with NGS results for HER2 and p53 Pearson r = 0.82 and 0.83, respectively. As half of GBC patients carry at least one potentially actionable molecular alteration, molecular testing may open the way to explore targeted therapy options for GBC patients.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Precis Oncol Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos