Chromosome 6p amplification in aqueous humor cell-free DNA is a prognostic biomarker for retinoblastoma ocular survival

Liya Xu, Ashley Polski, Rishvanth K. Prabakar, Mark W. Reid, Patricia Chevez-Barrios, Rima Jubran, Jonathan W. Kim, Peter Kuhn, David Cobrinik, James Hicks, Jesse L. Berry

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Aqueous humor contains tumor-derived cell-free DNA (cfDNA) and can serve as a liquid biopsy for retinoblastoma. We previously associated somatic copy-number alteration (SCNA) 6p gain with a 10-fold increased risk of enucleation. Here we provide a 2-year update to further explore 6p gain as a prognostic biomarker for ocular survival. Patients diagnosed with retinoblastoma from December 2014 to July 2019 from whom aqueous humor was sampled were included. cfDNA was extracted and shallow whole-genome sequencing performed to identify highly recurrent retinoblastoma SCNAs (gain of 1q, 2p, 6p, loss of 13q, 16q). 116 aqueous humor samples from 50 eyes of 46 patients were included: 27 eyes were salvaged, 23 were enucleated. Highly recurrent retinoblastoma SCNAs were found in 66% eyes. 6p gain was the most prevalent SCNA (50% eyes). It was particularly more prevalent in enucleated eyes (73.9%) than in salvaged eyes (29.6%; P ¼ 0.004). 6p gain in aqueous humor cfDNA portended nearly 10-fold increased odds of enucleation (OR ¼ 9.87; 95% confidence interval ¼ 1.75-55.65; P ¼ 0.009). In the enucleated eyes, 6p gain was associated with aggressive histopathologic features, including necrosis, higher degrees of anaplasia, and focal invasion of ocular structures. With extended follow-up and nearly double the aqueous humor samples, we continue to demonstrate 6p gain as a potential prognostic biomarker for retinoblastoma.

Original languageEnglish (US)
Pages (from-to)1166-1175
Number of pages10
JournalMolecular Cancer Research
Issue number8
StatePublished - Aug 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research


Dive into the research topics of 'Chromosome 6p amplification in aqueous humor cell-free DNA is a prognostic biomarker for retinoblastoma ocular survival'. Together they form a unique fingerprint.

Cite this