Analysis of the mutational status of SIX1/2 and microRNA processing genes in paired primary and relapsed Wilms tumors and association with relapse.

Autor: Ciceri S; Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Montalvão-de-Azevedo R; Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Pediatric Hematology-Oncology Research Program, Research Center (CPQ), Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., Tajbakhsh A; Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Medical Genetic and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran., Bertolotti A; Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Spagnuolo RD; Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Boschetti L; Pediatric Oncology Unit, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Capasso M; Department of Pediatric Oncology, Ospedale Santobono-Pausilipon, Naples, Italy., D'Angelo P; Pediatric Hematology and Oncology Unit, ARNAS Civico, Di Cristina e Benfratelli Hospitals, Palermo, Italy., Serra A; Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Pediatric Hospital and IRCCS, Rome, Italy., Diomedi-Camassei F; Pathology Unit, Department of Laboratories, Bambino Gesù Pediatric Hospital and IRCCS, Rome, Italy., Meli M; Unit of Pediatric Hematology and Oncology, Department of Clinical and Experimental Medicine, Hospital Policlinico, University of Catania, Catania, Italy., Nantron M; Department of Hematology and Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Quarello P; Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy., Buccoliero AM; Division of Pathology, Children's Hospital A. Meyer-University of Florence, Florence, Italy., Tamburini A; Hematology Oncology and HSCT Unit, Children's Hospital A.Meyer-University of Florence, Florence, Italy., Ciniselli CM; Bioinformatics and Biostatistics Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Verderio P; Bioinformatics and Biostatistics Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Collini P; Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Radice P; Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Spreafico F; Pediatric Oncology Unit, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Perotti D; Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. daniela.perotti@istitutotumori.mi.it.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2021 Sep; Vol. 28 (9), pp. 1016-1024. Date of Electronic Publication: 2020 Dec 06.
DOI: 10.1038/s41417-020-00268-3
Abstrakt: Whereas 90% of patients with Wilms tumor (WT) reach cure, approximately half of patients developing a recurrent tumor die of the disease. Therefore, to disclose events leading to recurrence represents a clinical need. To study paired primary/recurrent tumor samples, being aware of the intra-tumoral heterogeneity, might help finding these answers. We previously suggested that mutations in SIX1 and DROSHA underlie WT recurrence. With the aim to better investigate this scenario, we collected 19 paired primary/recurrent tumors and 10 primary tumors from relapsing patients and searched for mutations in the SIX1/2 genes and microRNA processing genes (miRNAPGs). We found SIX1 mutation in one case, miRNAPGs mutations in seven cases, and the co-occurrence of SIX1 and miRNAPG mutations in one case. We could observe that, whereas in primary tumors the mutations could be heterogeneously present, in all cases they were positively selected and homogeneously present in the recurrent disease, as also indicated by a "moderate" and "almost perfect" agreement (according to the Landis and Koch classification criteria) between paired samples. Analysis of SIX1/2 genes and miRNAPGs in 50 non-relapsing WTs disclosed SIX2 mutation in one case and miRNAPGs mutations in seven. A borderline statistically significant association was observed between miRNAPGs mutations and the occurrence of relapse (p value: 0.05). These data suggest that SIX1 and miRNAPGs mutations may provide an advantage during tumor progression to recurrence and can represent oncogenic drivers in WT development.
(© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)
Databáze: MEDLINE
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