Research Papers:

Whole-exome analysis in osteosarcoma to identify a personalized therapy

Caterina Chiappetta, Massimiliano Mancini, Francesca Lessi, Paolo Aretini, Veronica De Gregorio, Chiara Puggioni, Raffaella Carletti, Vincenzo Petrozza, Prospero Civita, Sara Franceschi, Antonio G. Naccarato, Carlo Della Rocca _, Chiara M. Mazzanti and Claudio Di Cristofano

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Oncotarget. 2017; 8:80416-80428. https://doi.org/10.18632/oncotarget.19010

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Caterina Chiappetta1, Massimiliano Mancini1, Francesca Lessi2, Paolo Aretini2, Veronica De Gregorio2, Chiara Puggioni1, Raffaella Carletti1, Vincenzo Petrozza1, Prospero Civita2, Sara Franceschi2, Antonio G. Naccarato3, Carlo Della Rocca1, Chiara M. Mazzanti2,* and Claudio Di Cristofano1,*

1UOC of Pathology, Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Latina, Italy

2Pisa Science Foundation, Pisa, Italy

3Department of Pathology, University of Pisa, Pisa, Italy

*These authors contributed equally to this work

Correspondence to:

Carlo Della Rocca, email: [email protected]

Keywords: osteosarcoma, next generation sequencing, carcinogenesis, metastasis, drug resistance

Received: March 31, 2017 Accepted: June 20, 2017 Published: July 05, 2017


Osteosarcoma is the most common pediatric primary non-hematopoietic bone tumor. Survival of these young patients is related to the response to chemotherapy and development of metastases. Despite many advances in cancer research, chemotherapy regimens for osteosarcoma are still based on non-selective cytotoxic drugs. It is essential to investigate new specific molecular therapies for osteosarcoma to increase the survival rate of these patients. We performed exomic sequence analyses of 8 diagnostic biopsies of patients with conventional high grade osteosarcoma to advance our understanding of their genetic underpinnings and to correlate the genetic alteration with the clinical and pathological features of each patient to identify a personalized therapy.

We identified 18,275 somatic variations in 8,247 genes and we found three mutated genes in 7/8 (87%) samples (KIF1B, NEB and KMT2C). KMT2C showed the highest number of variations; it is an important component of a histone H3 lysine 4 methyltransferase complex and it is one of the histone modifiers previously implicated in carcinogenesis, never studied in osteosarcoma. Moreover, we found a group of 15 genes that showed variations only in patients that did not respond to therapy and developed metastasis and some of these genes are involved in carcinogenesis and tumor progression in other tumors.

These data could offer the opportunity to get a key molecular target to identify possible new strategies for early diagnosis and new therapeutic approaches for osteosarcoma and to provide a tailored treatment for each patient based on their genetic profile.

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