Establishing the clinical utility of ctdna analysis for diagnosis, prognosis, and treatment monitoring of retinoblastoma: The aqueous humor liquid biopsy

Liya Xu, Mary E. Kim, Ashley Polski, Rishvanth K. Prabakar, Lishuang Shen, Chen Ching Peng, Mark W. Reid, Patricia Chévez-Barrios, Jonathan W. Kim, Rachana Shah, Rima Jubran, Peter Kuhn, David Cobrinik, Jaclyn A. Biegel, Xiaowu Gai, James Hicks, Jesse L. Berry

Research output: Contribution to journalArticlepeer-review

Abstract

Because direct tumor biopsy is prohibited for retinoblastoma (RB), eye-specific molecular biomarkers are not used in clinical practice for RB. Recently, we demonstrated that the aqueous humor (AH) is a rich liquid biopsy source of cell-free tumor DNA. Herein, we detail clinically-relevant molecular biomarkers from the first year of prospective validation data. Seven eyes from 6 RB patients who had AH sampled at diagnosis and throughout therapy with ≥12 months of follow-up were included. Cell-free DNA (cfDNA) from each sample was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs), followed by targeted resequencing for pathogenic variants using a RB1 and MYCN custom hybridization panel. Tumoral genomic information was detected in 100% of diagnostic AH samples. Of the seven diagnostic AH samples, 5/7 were positive for RB SCNAs. Mutational analysis identified RB1 variants in 5/7 AH samples, including the 2 samples in which no SCNAs were detected. Two eyes failed therapy and required enucleation; both had poor prognostic biomarkers (chromosome 6p gain or MYCN amplification) present in the AH at the time of diagnosis. In the context of previously established pre-analytical, analytical, and clinical validity, this provides evidence for larger, prospective studies to further establish the clinical utility of the AH liquid biopsy and its applications to precision oncology for RB.

Original languageEnglish (US)
Article number1282
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume13
Issue number6
DOIs
StatePublished - Mar 2 2021

Keywords

  • Aqueous humor
  • CtDNA
  • Liquid biopsy
  • Precision oncology
  • Retinoblastoma
  • SCNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Establishing the clinical utility of ctdna analysis for diagnosis, prognosis, and treatment monitoring of retinoblastoma: The aqueous humor liquid biopsy'. Together they form a unique fingerprint.

Cite this