Lorenz et al. published an extensive study investigating the genomic chaos in osteosarcoma

Susanne Lorenz
Susanne Lorenz

Susanne Lorenz has together with her colleagues at the Department for Tumor Biology and the Genomics Core Facility recently published an extensive genomic study of osteosarcoma in Oncotarget (journal impact factor 6.4). This study combined whole genome and transcriptome sequencing to unscramble the genomic chaos and its consequences.

The results revealed an extensive level of transcript fusions at the RNA level, the first reported recurrent fusion gene in osteosarcoma (PMP22-ELOVL5) and novel frequent aberration in TP53. Hundreds of genomic rearrangements were reported in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fusion transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which is further supported by typical trans-splicing characteristics. The most frequent aberrations were rearrangements involving TP53. The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors.


Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations.
Lorenz S, Barøy T, Sun J, Nome T, Vodák D, Bryne JC, Håkelien AM, Fernandez-Cuesta L, Möhlendick B, Rieder H, Szuhai K, Zaikova O, Ahlquist TC, Thomassen GO, Skotheim RI, Lothe RA, Tarpey PS, Campbell P, Flanagan A, Myklebost O, Meza-Zepeda LA.
Oncotarget. 2015 Dec PubMed

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Genomics Core Facility - Oslo University Hospital and Helse Sør-Øst