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Therapeutic implications of intratumor heterogeneity for TP53 mutational status in Burkitt lymphoma

Authors :
Pier Luigi Zinzani
Claudio Agostinelli
Andrea Ghelli Luserna di Rorà
Clelia Tiziana Storlazzi
Beatrice Casadei
Giovanni Martinelli
Stefano Pileri
Enrico Derenzini
Ilaria Iacobucci
Alberto L`Abbate
Enrica Imbrogno
A. Ferrari
Derenzini, Enrico
Iacobucci, Ilaria
Agostinelli, Claudio
Imbrogno, Enrica
Storlazzi, Clelia Tiziana
L`abbate, Alberto
Casadei, Beatrice
Ferrari, Anna
Ghelli Luserna Di Rorà, Andrea
Martinelli, Giovanni
Pileri, Stefano
Zinzani, Pier Luigi
ARTEC - AREA RAPPORTI IMPRESE, TERZA MISSIONE E COMUNICAZIONE WEB
DIPARTIMENTO DI FISICA E ASTRONOMIA 'AUGUSTO RIGHI'
DIPARTIMENTO DI INGEGNERIA DELL'ENERGIA ELETTRICA E DELL'INFORMAZIONE 'GUGLIELMO MARCONI'
DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE
Facolta' di MEDICINA e CHIRURGIA
Da definire
AREA MIN. 06 - Scienze mediche
Source :
Experimental Hematology & Oncology
Publisher :
Springer Nature

Abstract

none 12 no Therapeutic implications of intra-tumor heterogeneity are still undefined. In this study we report a genetic and functional analysis aimed at defining the mechanisms of chemoresistance in a 43-year old woman affected by stage IVB Burkitt lymphoma with bulky abdominal masses and peritoneal effusion. The patient, despite a transient initial response to chemotherapy with reduction of the bulky masses, rapidly progressed and died of her disease. Targeted TP53 sequencing found that the bulky mass was wild-type whereas peritoneal fluid cells harbored a R282W mutation. Functional studies on TP53 mutant cells demonstrated an impaired p53-mediated response, resistance to ex vivo doxorubicin administration, overexpression of DNA damage response (DDR) activation markers and high sensitivity to pharmacologic DDR inhibition. These findings suggest that intra-tumor heterogeneity for TP53 mutational status may occur in MYC-driven cancers, and that DDR inhibitors could be effective in targeting hidden TP53 mutant clones in tumors characterized by genomic instability and prone to intra-tumor heterogeneity. none Derenzini, Enrico; Iacobucci, Ilaria; Agostinelli, Claudio; Imbrogno, Enrica; Storlazzi, Clelia Tiziana; L`abbate, Alberto; Casadei, Beatrice; Ferrari, Anna; Ghelli Luserna Di Rorà, Andrea; Martinelli, Giovanni; Pileri, Stefano; Zinzani, Pier Luigi Derenzini, Enrico; Iacobucci, Ilaria; Agostinelli, Claudio; Imbrogno, Enrica; Storlazzi, Clelia Tiziana; L`abbate, Alberto; Casadei, Beatrice; Ferrari, Anna; Ghelli Luserna Di Rorà, Andrea; Martinelli, Giovanni; Pileri, Stefano; Zinzani, Pier Luigi

Details

Language :
English
ISSN :
21623619
Volume :
4
Issue :
1
Database :
OpenAIRE
Journal :
Experimental Hematology & Oncology
Accession number :
edsair.doi.dedup.....ffdb847d395e242ff766fc3518784bd2
Full Text :
https://doi.org/10.1186/s40164-015-0019-9