@article{7b5ed4533cc74a29afe5ba612bcf075a,
title = "A Comprehensive Circulating Tumor DNA Assay for Detection of Translocation and Copy-Number Changes in Pediatric Sarcomas",
abstract = "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.",
author = "Shah, {Avanthi Tayi} and Azad, {Tej D.} and Breese, {Marcus R.} and Chabon, {Jacob J.} and Hamilton, {Emily G.} and Krystal Straessler and Kurtz, {David M.} and Leung, {Stanley G.} and Aviv Spillinger and Liu, {Heng Yi} and Behroozfard, {Inge H.} and Wittber, {Frederick M.} and Hazard, {Florette K.} and Cho, {Soo Jin} and Daldrup-Link, {Heike E.} and Vo, {Kieuhoa T.} and Arun Rangaswami and Allison Pribnow and Spunt, {Sheri L.} and Lacayo, {Norman J.} and Maximilian Diehn and Alizadeh, {Ash A.} and Sweet-Cordero, {E. Alejandro}",
note = "Funding Information: D.M.Kurtz reports personal feesfromRoche Molecular Diagnostics, Genentech; and other support from Foresight Diagnostics outside the submitted work; in addition, D.M. Kurtz has a patent for Blood-based early detection of cancer pending and a patent for Ultrasensitive Cancer Monitoring by Phased variant Enrichment Sequencing pending. F.K. Hazard reports grants from United Therapeutics Corporation outside the submitted work. S.L. Spunt reports grants from Bayer AG, LOXO Oncology; and Funding Information: A.T. Shah was a Debra and Andrew Rachleff endowed fellow and was also funded by a St. Baldrick{\textquoteright}s Research Fellowship Grant, the Alex{\textquoteright}s Lemonade Stand Foundation, and the Frank A. Campini Foundation. T.D. Azad was funded by a Doris Duke Clinical Research Mentorship Award. H.E. Daldrup-Link was funded by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, R01 HD081123A). E.A. Sweet-Cordero was funded by a grant from the Alex{\textquoteright}s Lemonade Stand Foundation, the Child Health Research Institute (CHRI, Stanford), and the Children{\textquoteright}s Oncology Group Solid Malignancy-Integrated Translational Science Center. Additional funding was provided by the Lucile Packard Children{\textquoteright}s Hospital (Stanford University) and the Helen Diller Family Comprehensive Cancer Center (University of California San Francisco). This work used resources provided by the Stanford Genetics Bioinformatics Service Center and the Stanford Functional Genomics Facility, including those funded with support from an NIH S10 Shared Instrumentation Grant (S10OD018220). This work also used resources provided by the UCSF Center for Advanced Technology. The artwork for Fig. 1A was designed by Sarah Pyle. We thank the Stanford Tissue Bank and UCSF Tissue Bank for help collecting patient samples. We also thank all members of the Sweet-Cordero lab for their input and thoughtful discussion. We are especially grateful to all the patients and their families, who generously agreed to share blood and tumor samples to make this work possible. Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",
year = "2021",
month = oct,
doi = "10.1158/1535-7163.MCT-20-0987",
language = "English (US)",
volume = "20",
pages = "2016--2025",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "10",
}