Analysis of the mutational status of SIX1/2 and microRNA processing genes in paired primary and relapsed Wilms tumors and association with relapse
| Autor: | Chiara Maura Ciniselli, Paola Quarello, Francesca Diomedi-Camassei, Daniela Perotti, Rafaela Montalvão-de-Azevedo, Rosalin Dolores Spagnuolo, Filippo Spreafico, Paolo Verderio, Annalisa Serra, Mariaclaudia Meli, Sara Ciceri, Anna Maria Buccoliero, Paolo Radice, Angela Tamburini, Luna Boschetti, Paola Collini, Alessia Bertolotti, Amir Tajbakhsh, Maria Capasso, Marilina Nantron, Paolo D'Angelo |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Nerve Tissue Proteins Disease medicine.disease_cause Wilms Tumor 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Mutational status Humans Molecular Biology Gene Drosha Homeodomain Proteins Mutation business.industry Wilms' tumor medicine.disease Survival Analysis MicroRNAs 030104 developmental biology Tumor progression 030220 oncology & carcinogenesis Molecular Medicine business MicroRNA processing |
| Zdroj: | Cancer gene therapy. 28(9) |
| ISSN: | 1476-5500 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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