AI Article Synopsis

  • The study explores the origins of secondary gliosarcoma (SGS) that develops after treatment for primary glioblastoma multiforme (GBM), focusing on the uncharacterized clonal evolution of its sarcomatous components.
  • Researchers used whole-genome and deep-whole-exome sequencing to analyze mutations in both GBM and SGS, identifying specific mutations shared between the two tumors, particularly in tumor-suppressor genes NF1 and TP53.
  • Findings suggest that SGS likely arises from a single clonal origin influenced by mutations due to radiation therapy, indicating a causal link between radiotherapy and the emergence of SGS sarcomatous components.

Article Abstract

Aims: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy.

Methods: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis.

Results: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy.

Conclusions: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611784PMC
http://dx.doi.org/10.1111/cns.13740DOI Listing

Publication Analysis

Top Keywords

sgs
13
secondary gliosarcoma
12
sarcomatous components
12
clonal evolution
8
primary glioblastoma
8
sgs sarcomatous
8
components remain
8
gbm sgs
8
case sgs
8
gbm
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!