Adding the Cancer Genome Atlas Chromosome Classes to American Joint Committee on Cancer System Offers More Precise Prognostication in Uveal Melanoma

Gelmi, Maria Chiara; Baş, Zeynep; Malkani, K; Ganguly, Arupa; Shields, Carol L.; Jager, Martine J.

doi:10.1016/j.ophtha.2021.11.018

Cited by 26 publications

(15 citation statements)

References 29 publications

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“…Cytogenetic characteristics include highly recurrent UM SCNAs such as monosomy 3, losses of chromosome arms 1p, 6q, 8p, and 16q, and gains of 1q, 6p, and 8q [ 6 ], with monosomy 3, 8q gain, and 1p loss being the most prognostically unfavorable [ 7 ]. Although the American Joint Committee on Cancer (AJCC) staging of UM does not currently include cytogenetic information and is based only on clinical observations, it has been shown that the addition of these molecular subsets yields a significant improvement in prognostication compared to the AJCC stage alone [ 8 , 9 , 10 , 11 , 12 ]. While FNAB is considered a safe procedure, there remain small risks of retinal detachment, subretinal hemorrhage, and vitreous hemorrhage, sometimes requiring further surgical intervention to repair [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma

Peng

et al. 2022

IJMS

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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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Section: Introductionmentioning

confidence: 99%

Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma

Peng

et al. 2022

IJMS

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“…We believe that incorporation of tumor size into the GEP prediction algorithm will improve on its patient specific prediction. 10,16,22,27,32…”

Section: Discussionmentioning

confidence: 99%

Predicted vs Observed Metastasis-Free Survival in Individuals With Uveal Melanoma

et al. 2022

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the predicted metastasis-free survival (MFS) by a commercially available gene expression profiling (GEP) test is not known. OBJECTIVE To compare the predicted MFS with the observed MFS in patients in this cohort and with those in published studies (published MFS, meta-analysis). DESIGN, SETTING, AND PARTICIPANTSThis cohort study included consecutive patients from the University of Iowa and Cleveland Clinic who were diagnosed with uveal melanoma who underwent prognostic fine-needle aspiration biopsy at the time of primary treatment. Patients were recruited from December 2012 to December 2020. The predicted MFS for patients was extracted from the GEP report. The observed MFS was defined as time to metastasis. Cox proportional hazards models were fit to identify tumor variables impacting MFS in patients with class 2 tumors. The overall estimate of the published MFS was obtained by performing meta-analysis of data from published series. Analysis took place in August 2021. MAIN OUTCOMES AND MEASURES MFS.RESULTS There were 92 patients from the University of Iowa and 255 patients from the Cleveland Clinic. The mean (SD) age at diagnosis was 59.4 (13.0) years. The median (IQR) follow-up interval was 38.0 (19.0-57.0) months. The observed MFS for patients with class 2 tumor in this cohort (3 years: 67% [95% CI, 59%-77%]; 5 years: 47% [95% CI, 37%-61%]) and in published studies (3 years: 62% [95% CI, 57%-66%]; 5 years: 40% [95% CI, 34%-46%]) were better than those predicted (50% and 28% for 3 and 5 years, respectively). Within patients with class 2 tumor, those with metastasis had larger tumors compared with nonmetastatic tumors (mean largest basal diameter difference, 1.7 [95% CI, 0.5-3.0] mm; P = .01; mean thickness ratio, 1.3 [95% CI, 1.04-1.5]; P = .01, respectively). An increasing tumor size was significantly associated with increased hazard ratio (1.16 [95% CI, 1.06-1.27]; P < .001) of metastasis.CONCLUSIONS AND RELEVANCE These findings suggest the predicted MFS for metastatic tumors (class 2) appears to be worse than that observed here and reported by others. Incorporation of tumor size in the prediction model may enhance its accuracy. Adjuvant therapy trials may not be able to rely on predicted MFS to calculate efficacy with a high degree of confidence.

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“…CM tissues were resected from patients with clinically and pathologically diagnosed CM. In details, inclusion criteria of the patient are shown as below: (1) with high suspicion of choroidal melanoma based on clinical imaging data and clinical ophthalmological examination; (2) absence of other pathologies;…”

Section: Specimen Preparation and Data Collectionmentioning

confidence: 99%

“…Choroidal melanoma (CM) is an intraocular malignancy commonly occurring in adults, with 90%–95% of cases arising from the choroid 1 . CM can potentially metastasize to various organs/tissues, including the liver, soft tissues, bone, lung, skin and lymph nodes 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Choroidal melanoma (CM) is an intraocular malignancy commonly occurring in adults, with 90%–95% of cases arising from the choroid. 1 CM can potentially metastasize to various organs/tissues, including the liver, soft tissues, bone, lung, skin and lymph nodes. 2 The prognosis of CM is characterized by high rates of mortality and metastasis; however, the mechanism of metastasis in CM is unclear.…”

Section: Introductionmentioning

confidence: 99%

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METTL14 promotes migration and invasion of choroidal melanoma by targeting RUNX2 mRNA via m6A modification

Zhang

Liu

et al. 2022

J Cellular Molecular Medi

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BackgroundAlthough the modi cation of N6-methyladenosine is involved in the progression of a variety of cancers, the associated regulatory mechanism underlying the progression of choroidal melanoma remains poorly understood. MethodsIn this study, we aimed to investigate the mechanism of N6-methyladenosine in the pathogenesis of choroidal melanoma. The expression level of methyltransferase-like 14 in choroidal melanoma tissues was determined using western blot analysis and immunohistochemistry, and compared with that in normal choroidal tissues. Next, the impacts of methyltransferase-like 14 on invasion and migration of choroidal melanoma cells were determined using functional and animal experiments. The interaction between methyltransferase-like 14 and its downstream target was identi ed by methylated RNA immunoprecipitation and a dual-luciferase reporter assay. Additionally, protein expression of factors related to the Wnt/β-catenin signaling pathway was evaluated by western blot analysis. ResultsMethyltransferase-like 14 was upregulated in choroidal melanoma tissues in comparison with that in normal choroidal tissues. Overexpression and knockdown of methyltransferase-like 14 enhanced and inhibited the invasion and migration of choroidal melanoma cells, respectively, both in vivo and in vitro. Methyltransferase-like 14 directly targeted downstream runt-related transcription factor 2 mRNA, and this effect was dependent on N6-methyladenosine. Additionally, the Wnt/β-catenin signaling pathway was activated by methyltransferase-like 14 in choroidal melanoma cells. ConclusionsOur study identi ed a novel RNA regulatory mechanism in which runt-related transcription factor 2 was upregulated by enhanced expression of methyltransferase-like 14 via N6-methyladenosine modi cation, thus facilitating migration and invasion of choroidal melanoma cells.

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Adding the Cancer Genome Atlas Chromosome Classes to American Joint Committee on Cancer System Offers More Precise Prognostication in Uveal Melanoma

Cited by 26 publications

References 29 publications

Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma

Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma

Predicted vs Observed Metastasis-Free Survival in Individuals With Uveal Melanoma

METTL14 promotes migration and invasion of choroidal melanoma by targeting RUNX2 mRNA via m6A modification

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