ABSTRACT
PURPOSE: Clinical sequencing of tumor DNA is necessary to render an integrated diagnosis and select therapy for children with primary central nervous system (CNS) tumors, but neurosurgical biopsy is not without risk. In this study, we describe cell-free DNA (cfDNA) in blood and cerebrospinal fluid (CSF) as sources for "liquid biopsy" in pediatric brain tumors. METHODS: CSF samples were collected by lumbar puncture, ventriculostomy, or surgery from pediatric patients with CNS tumors. Following extraction, CSF-derived cfDNA was sequenced using UW-OncoPlex™, a clinically validated next-generation sequencing platform. CSF-derived cfDNA results and paired plasma and tumor samples concordance was also evaluated. RESULTS: Seventeen CSF samples were obtained from 15 pediatric patients with primary CNS tumors. Tumor types included medulloblastoma (n = 7), atypical teratoid/rhabdoid tumor (n = 2), diffuse midline glioma with H3 K27 alteration (n = 4), pilocytic astrocytoma (n = 1), and pleomorphic xanthoastrocytoma (n = 1). CSF-derived cfDNA was detected in 9/17 (53%) of samples, and sufficient for sequencing in 8/10 (80%) of extracted samples. All somatic mutations and copy-number variants were also detected in matched tumor tissue, and tumor-derived cfDNA was absent in plasma samples and controls. Tumor-derived cfDNA alterations were detected in the absence of cytological evidence of malignant cells in as little as 200 µl of CSF. Several clinically relevant alterations, including a KIAA1549::BRAF fusion were detected. CONCLUSIONS: Clinically relevant genomic alterations are detectable using CSF-derived cfDNA across a range of pediatric brain tumors. Next-generation sequencing platforms are capable of producing a high yield of DNA alterations with 100% concordance rate with tissue analysis.
Subject(s)
Biomarkers, Tumor , Brain Neoplasms , Circulating Tumor DNA , High-Throughput Nucleotide Sequencing , Humans , Child , Brain Neoplasms/genetics , Brain Neoplasms/cerebrospinal fluid , Brain Neoplasms/diagnosis , Male , Female , Child, Preschool , Adolescent , Infant , Circulating Tumor DNA/cerebrospinal fluid , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , High-Throughput Nucleotide Sequencing/methods , Biomarkers, Tumor/genetics , Biomarkers, Tumor/cerebrospinal fluid , Cell-Free Nucleic Acids/cerebrospinal fluid , Cell-Free Nucleic Acids/genetics , Cell-Free Nucleic Acids/blood , Liquid Biopsy/methods , MutationABSTRACT
INTRODUCTION: Survivors of cancer are at risk for adverse mental and physical health outcomes. It is not well understood, however, how these outcomes are differentially experienced according to an individual's exposure to racism. This study sought to evaluate associations of race/ethnicity, and experiences of racism, with adverse health outcomes in survivors of cancer. METHODS: Using the Behavioral Risk Factor Surveillance System database, data from 48,200 survivors between 2014 and 2020 were evaluated. Survey items included negative physical and emotional symptoms as a result of race-based treatment. Outcomes of interest included days of poor mental and physical health, activity limitations, depression, and inadequate sleep. Associations using prevalence ratios were evaluated. RESULTS: All historically marginalized racial/ethnic groups were more likely to experience at least one adverse health outcome compared with non-Hispanic White survivors. Those who physically experienced racism were 2.1 (95% CI, 1.64-2.69) times as likely to report poor physical health, 3.51 (95% CI, 2.61-4.71) times as likely to report poor mental health, 2.14 (95% CI, 1.77-2.58) times as likely to report inadequate sleep, 2.33 (95% CI: 1.91-2.83) times as likely to report depression, and 1.42 (95% CI, 1.04-1.93) times as likely to report activity limitations compared with those who have not experienced racism. Similar associations were observed for emotionally experienced racism. DISCUSSION: Racial inequities in health outcomes for survivors of cancer from marginalized racial/ethnic groups are well-established. Experienced racism contributes to adverse health outcomes and widens these disparities. Improving outcomes for survivors of cancer may require screening for experienced racism. PLAIN LANGUAGE SUMMARY: Survivors of cancer from marginalized racial/ethnic populations are more likely to have poor mental and physical health than their non-Hispanic White counterparts. Whether survivors from certain racial/ethnic populations of smaller size also have poorer health is less well understood. Generally, individuals who report experienced racism also report poor health, this association has not been studied in survivors of cancer. This study, from a national survey of survivors of cancer, describes disparities in health outcomes experienced by a variety of racial and ethnic populations. Our findings suggest racism is associated with poor mental and physical health in survivors of cancer.
