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Leiomyosarcomas

whole genome sequencing for a whole biology characterization

Chibon, Frédérica,b; Darbo, Elodiec,d; Pérot, Gaëllea,e

doi: 10.1097/CCO.0000000000000550
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Purpose of review Leiomyosarcoma (LMS) is among the more aggressive sarcomas and still suffers from the lack of efficient systemic treatment after, or before, surgery. During the last decades, one provider of therapeutic improvement has been the targeting of genome alterations. Efforts have thus been done to apply next-generation sequencing approaches to those tumours to decipher their oncogenesis and find out such targets.

Recent findings Sequencing performed so far, based on exome, mostly confirmed that p53 and RB1 are the two main pathways altered in LMS oncogenesis. There are few point mutations in LMS genome, which is mainly characterized by numerous chromosomal rearrangements. Data from whole genome sequencing are now mandatory to decipher mechanisms triggering chromosomal instability and mutational process.

Summary Although each LMS appears to have quite private genetic alterations leading to oncogenesis, it is likely that the altered biological pathways are relatively homogeneous within each of the LMS subgroups. Understanding this oncogenesis, thanks to integrated approaches involving whole genome and transcriptome sequencing together with functional and clinical characterizations will certainly give us the keys to relevant and effective new therapeutic approaches.

aINSERM U1037, Cancer Research Center in Toulouse (CRCT)

bDepartment of Pathology, Institut Claudius Régaud, IUCT-Oncopole, Toulouse

cINSERM U1218

dUniversity of Bordeaux, Bordeaux

eDepartment of Pathology, CHU de Toulouse – Oncopole, Université de Toulouse, Toulouse, France

Correspondence to Frédéric Chibon, Eq-19: ONCOSARC, CRCT/IUCT-ONCOPOLE, UMR1037 INSERM-Université Toulouse 3 - ERL5294 CNRS, 2 avenue Hubert Curien, CS 53717, 31037 TOULOUSE CEDEX 1, France. E-mail: frederic.chibon@inserm.fr

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