BRIEF RESEARCH REPORT article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1632580
Genomic trajectories of colorectal cancer with choroidal metastasis: longitudinal insights from tissue and liquid biopsy via next-generation sequencing
Provisionally accepted
Alessandro Ottaiano1
Luisa Circelli2Carmine Picone3Monica Ianniello2Raffaella Ruggiero2
Roberto Sirica2
Mariachiara Santorsola3Anna Chiara Carratù3Nadia Petrillo2Gaetana Cerbone4
Francesco Sabbatino5Massimiliano Berretta6
Guglielmo Nasti3Giovanni Savarese2*- 1IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - Napoli, Naples, Italy
- 2AMES Multi-specialty Diagnostic Center Srl, Casalnuovo di Napoli, Italy
- 3IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - Napoli, Naples, Campania, Italy
- 4San Giuseppe Moscati Hospital of National Importance and High Specialty, Avellino, Campania, Italy
- 5University of Salerno, Fisciano, Campania, Italy
- 6University of Messina, Messina, Sicilia, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Colorectal cancer (CRC) is a leading cause of cancer-related death, with metastases typically involving the liver, lungs, and peritoneum. Choroidal metastases are extremely rare. We report a case of metastatic CRC with choroidal involvement, characterized by longitudinal genomic profiling using the TruSight Oncology 500® assay. A 66-year-old man with rectosigmoid junction CRC initially showed RAS/BRAF wild-type status, microsatellite stability (MSS), and a moderate tumor mutational burden (TMB: 7.1 mutations/Mb) on the primary tumor. First-line chemotherapy combined with anti-EGFR therapy was initiated for synchronous liver metastases. Upon the development of visual symptoms, imaging confirmed choroidal metastasis. Circulating tumor DNA (ctDNA) analysis revealed persistence of the TP53 p.E286K mutation and marked clonal evolution. Newly emerged Tier IA alterations included EGFR amplification and JAK2 p.V617F mutation, alongside multiple Tier IIC and IID variants absent in the primary tumor. The ctDNA also revealed a hypermutated phenotype (TMB: 44.9 mutations/Mb). To our knowledge, this is the first report integrating both tissue- and liquid-based NGS in a CRC case with ocular metastasis. These findings highlight the value of comprehensive genomic monitoring in metastatic CRC and may offer insights into the molecular landscape of rare metastatic sites such as the choroid.
Keywords: Choroidal metastasis, Next-generation sequencing, Circulating tumour DNA, tumour heterogeneity, Colorecal cancer
Received: 21 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Ottaiano, Circelli, Picone, Ianniello, Ruggiero, Sirica, Santorsola, Carratù, Petrillo, Cerbone, Sabbatino, Berretta, Nasti and Savarese. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Giovanni Savarese, AMES Multi-specialty Diagnostic Center Srl, Casalnuovo di Napoli, 80013, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.