Genomic Profiling of Uterine Aspirates and cfDNA as an Integrative Liquid Biopsy Strategy in Endometrial Cancer
Casas-Arozamena, Carlos (Instituto de Investigación Sanitaria de Santiago (IDIS))
Diaz, Eva (Foundation MD Anderson International (Madrid))
Moiola, Cristian Pablo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Alonso-Alconada, Lorena (Nasasbiotech (La Coruña))
Ferreiros, Alba (Nasasbiotech (La Coruña))
Abalo, Alicia (Instituto de Investigación Sanitaria de Santiago (IDIS))
López Gil, Carlos (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Oltra, Sara S. (Foundation MD Anderson International (Madrid))
de Santiago, Javier (Department of Gynecology, MD Anderson Cancer Center, 28029 Madrid, Spain)
Cabrera Díaz, Silvia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sampayo, Victoria (Complejo Hospitalario Universitario de Santiago de Compostela)
Bouso, Marta (Complejo Hospitalario Universitario de Santiago de Compostela)
Arias, Efigenia (Complejo Hospitalario Universitario de Santiago de Compostela)
Cueva, Juan (Instituto de Investigación Sanitaria de Santiago (IDIS))
Colás Ortega, Eva (Centro de Investigación Biomédica en Red de Cáncer)
Vilar, Ana (Complejo Hospitalario Universitario de Santiago de Compostela)
Gil-Moreno, Antonio 1965- (Centro de Investigación Biomédica en Red de Cáncer)
Abal Posada, Miguel (Centro de Investigación Biomédica en Red de Cáncer)
Moreno-Bueno, Gema (University of Madrid)
Muinelo-Romay, Laura (Centro de Investigación Biomédica en Red de Cáncer)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, we combined different types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41. 2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38. 9% of patients were positive for CTCs at surgery. Finally, the efficacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapies.
Grants:	Instituto de Salud Carlos III PI17/01919 Instituto de Salud Carlos III PI17/02071 Ministerio de Economía y Competitividad CB16/12/00328 Ministerio de Economía y Competitividad PI16/00134 Ministerio de Economía y Competitividad CB16/12/00295
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Endometrial cancer ; Uterine aspirates ; Circulating biomarkers ; Circulating tumor DNA (ctDNA) ; Circulating tumor cells (CTCs) ; PDX models ; Targeted therapies
Published in:	Journal of clinical medicine, Vol. 9 (february 2020) , ISSN 2077-0383

DOI: 10.3390/jcm9020585
PMID: 32098121

16 p, 3.4 MB

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