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Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma

Tumor biopsy can identify prognostic biomarkers for metastatic uveal melanoma (UM), however aqueous humor (AH) liquid biopsy may serve as an adjunct. This study investigated whether the AH of UM eyes has sufficient circulating tumor DNA (ctDNA) to perform genetic analysis. This is a case series of 3...

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Autores principales: Im, Deborah H., Peng, Chen-Ching, Xu, Liya, Kim, Mary E., Ostrow, Dejerianne, Yellapantula, Venkata, Bootwalla, Moiz, Biegel, Jaclyn A., Gai, Xiaowu, Prabakar, Rishvanth K., Kuhn, Peter, Hicks, James, Berry, Jesse L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181140/
https://www.ncbi.nlm.nih.gov/pubmed/35682905
http://dx.doi.org/10.3390/ijms23116226
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author Im, Deborah H.
Peng, Chen-Ching
Xu, Liya
Kim, Mary E.
Ostrow, Dejerianne
Yellapantula, Venkata
Bootwalla, Moiz
Biegel, Jaclyn A.
Gai, Xiaowu
Prabakar, Rishvanth K.
Kuhn, Peter
Hicks, James
Berry, Jesse L.
author_facet Im, Deborah H.
Peng, Chen-Ching
Xu, Liya
Kim, Mary E.
Ostrow, Dejerianne
Yellapantula, Venkata
Bootwalla, Moiz
Biegel, Jaclyn A.
Gai, Xiaowu
Prabakar, Rishvanth K.
Kuhn, Peter
Hicks, James
Berry, Jesse L.
author_sort Im, Deborah H.
collection PubMed
description Tumor biopsy can identify prognostic biomarkers for metastatic uveal melanoma (UM), however aqueous humor (AH) liquid biopsy may serve as an adjunct. This study investigated whether the AH of UM eyes has sufficient circulating tumor DNA (ctDNA) to perform genetic analysis. This is a case series of 37 AH samples, taken before or after radiation, and one tumor wash sample, from 12 choroidal and 8 ciliary body (CB) melanoma eyes. AH was analyzed for nucleic acid concentrations. AH DNA and one tumor wash sample underwent shallow whole-genome sequencing followed by Illumina sequencing to detect somatic copy number alterations (SCNAs). Four post-radiation AH underwent targeted sequencing of BAP1 and GNAQ genes. Post-radiation AH had significantly higher DNA and miRNA concentrations than paired pre-radiation samples. Highly recurrent UM SCNAs were identified in 0/11 post-radiation choroidal and 6/8 post-radiation CB AH. SCNAs were highly concordant in a CB post-radiation AH with its matched tumor (r = 0.978). BAP1 or GNAQ variants were detected in 3/4 post-radiation AH samples. AH is a source of ctDNA in UM eyes, particularly in post-radiation CB eyes. For the first time, UM SCNAs and mutations were identified in AH-derived ctDNA. Suggesting that AH can serve as a liquid biopsy for UM.
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spelling pubmed-91811402022-06-10 Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma Im, Deborah H. Peng, Chen-Ching Xu, Liya Kim, Mary E. Ostrow, Dejerianne Yellapantula, Venkata Bootwalla, Moiz Biegel, Jaclyn A. Gai, Xiaowu Prabakar, Rishvanth K. Kuhn, Peter Hicks, James Berry, Jesse L. Int J Mol Sci Article Tumor biopsy can identify prognostic biomarkers for metastatic uveal melanoma (UM), however aqueous humor (AH) liquid biopsy may serve as an adjunct. This study investigated whether the AH of UM eyes has sufficient circulating tumor DNA (ctDNA) to perform genetic analysis. This is a case series of 37 AH samples, taken before or after radiation, and one tumor wash sample, from 12 choroidal and 8 ciliary body (CB) melanoma eyes. AH was analyzed for nucleic acid concentrations. AH DNA and one tumor wash sample underwent shallow whole-genome sequencing followed by Illumina sequencing to detect somatic copy number alterations (SCNAs). Four post-radiation AH underwent targeted sequencing of BAP1 and GNAQ genes. Post-radiation AH had significantly higher DNA and miRNA concentrations than paired pre-radiation samples. Highly recurrent UM SCNAs were identified in 0/11 post-radiation choroidal and 6/8 post-radiation CB AH. SCNAs were highly concordant in a CB post-radiation AH with its matched tumor (r = 0.978). BAP1 or GNAQ variants were detected in 3/4 post-radiation AH samples. AH is a source of ctDNA in UM eyes, particularly in post-radiation CB eyes. For the first time, UM SCNAs and mutations were identified in AH-derived ctDNA. Suggesting that AH can serve as a liquid biopsy for UM. MDPI 2022-06-02 /pmc/articles/PMC9181140/ /pubmed/35682905 http://dx.doi.org/10.3390/ijms23116226 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Im, Deborah H.
Peng, Chen-Ching
Xu, Liya
Kim, Mary E.
Ostrow, Dejerianne
Yellapantula, Venkata
Bootwalla, Moiz
Biegel, Jaclyn A.
Gai, Xiaowu
Prabakar, Rishvanth K.
Kuhn, Peter
Hicks, James
Berry, Jesse L.
Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma
title Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma
title_full Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma
title_fullStr Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma
title_full_unstemmed Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma
title_short Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma
title_sort potential of aqueous humor as a liquid biopsy for uveal melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181140/
https://www.ncbi.nlm.nih.gov/pubmed/35682905
http://dx.doi.org/10.3390/ijms23116226
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