A Comprehensive Circulating Tumor DNA Assay for Detection of Translocation and Copy-Number Changes in Pediatric Sarcomas

Avanthi Tayi Shah, Tej D. Azad, Marcus R. Breese, Jacob J. Chabon, Emily G. Hamilton, Krystal Straessler, David M. Kurtz, Stanley G. Leung, Aviv Spillinger, Heng Yi Liu, Inge H. Behroozfard, Frederick M. Wittber, Florette K. Hazard, Soo Jin Cho, Heike E. Daldrup-Link, Kieuhoa T. Vo, Arun Rangaswami, Allison Pribnow, Sheri L. Spunt, Norman J. LacayoMaximilian Diehn, Ash A. Alizadeh, E. Alejandro Sweet-Cordero

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Most circulating tumor DNA (ctDNA) assays are designed to detect recurrent mutations. Pediatric sarcomas share few recurrent mutations but rather are characterized by translocations and copy-number changes. We applied Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for detection of translocations found in the most common pediatric sarcomas. We also applied ichorCNA to the combined off-target reads from our hybrid capture to simultaneously detect copy-number alterations (CNA). We analyzed 64 prospectively collected plasma samples from 17 patients with pediatric sarcoma. Translocations were detected in the pretreatment plasma of 13 patients and were confirmed by tumor sequencing in 12 patients. Two of these patients had evidence of complex chromosomal rearrangements in their ctDNA. We also detected copy-number changes in the pretreatment plasma of 7 patients. We found that ctDNA levels correlated with metastatic status and clinical response. Furthermore, we detected rising ctDNA levels before relapse was clinically apparent, demonstrating the high sensitivity of our assay. This assay can be utilized for simultaneous detection of translocations and CNAs in the plasma of patients with pediatric sarcoma. While we describe our experience in pediatric sarcomas, this approach can be applied to other tumors that are driven by structural variants.

Original languageEnglish (US)
Pages (from-to)2016-2025
Number of pages10
JournalMolecular Cancer Therapeutics
Issue number10
StatePublished - Oct 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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