Abstract

PURPOSE/OBJECTIVE(S): Radiation-induced sarcoma (RIS) is a rare secondary malignancy resulting from ionizing radiation-related treatment after a long latency period. Despite the unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them.

MATERIALS/METHODS: We performed whole-genome sequencing (WGS) of 11 cases of RIS matched with normal genomes to identify somatic alterations potentially associated with RIS development.

RESULTS: The mutation abundance of RIS genomes including one hypermutated genome was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations (SVs). The effects of non-homologous end joining on short insertions-deletions and SVs were substantial in RIS genomes, compared with in spontaneous osteosarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis and predisposing germline variants in DNA damage-repair pathways were identified.

CONCLUSION: Taken together, WGS-scale characterization of RIS genomes may pave the way for advanced diagnostic and therapeutic strategies for RIS.

Original languageEnglish
Pages (from-to)e241-e242
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume111
Issue number3S
DOIs
StatePublished - 1 Nov 2021

Bibliographical note

Copyright © 2021. Published by Elsevier Inc.

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