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Integrative genomic and transcriptomic analysis of adult leiomyosarcoma (HIPO-028, HIPO-018, HIPO-021)

Leiomyosarcoma (LMS) is an aggressive mesenchmyal malignancy with few therapeutic options. The mechanisms underlying LMS development, including clinically actionable genetic vulnerabilities, are largely unknown. We performed genomic and transcriptomic profiling of a large cohort of LMS tumors and identified substantial mutational heterogeneity, near-universal inactivation of TP53 and RB1, widespread DNA copy number alterations, chromothripsis, and frequent whole-genome duplication. Furthermore, we discovered recurrent alterations in telomere maintenance genes such as ATRX, RBL2, and RPA1, resulting in alternative lengthening of telomeres in 78% of cases. Finally, most tumors displayed hallmarks of “BRCAness”, including alterations in various homologous recombination DNA repair genes, multiple structural rearrangements, and enrichment of specific mutational signatures, and cultured LMS cells were sensitive towards olaparib and cisplatin treatment. This first comprehensive study of genetic alterations in LMS has uncovered key biological features that may inform future experimental research and enable the design of novel therapeutic strategies for this disease.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003827 HiSeq X Ten 4
EGAD00001003828 Illumina HiSeq 2000 Illumina HiSeq 2500 37
EGAD00001003829 Illumina HiSeq 2000 Illumina HiSeq 2500 96
Publications Citations
Integrative genomic and transcriptomic analysis of leiomyosarcoma.
Nat Commun 9: 2018 144
TelomereHunter - in silico estimation of telomere content and composition from cancer genomes.
BMC Bioinformatics 20: 2019 272
Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations.
J Transl Med 19: 2021 204