Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients

Lally, Sara E.; Milman, Tatyana; Orloff, Marlana; Dalvin, Lauren A; Eberhart, Charles G.; Heaphy, Christopher M.; Rodríguez, Fausto J.; Lin, Chun-Chieh; Dockery, Philip W.; Shields, Jerry A.; Shields, Carol L.

doi:10.1016/j.ophtha.2022.01.016

Cited by 23 publications

(47 citation statements)

References 47 publications

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“…evaluated genetic mutations and molecular genetic pathways in CM and reported that loss of ATRX and ALT may be early events in CM. They also confirmed that NRAS mutation implied an increased risk for metastasis and death in CM ( 44 ). Though mutations are frequently present in CM, little is known about prognostic genetic biomarkers due to the low incidence of this disease.…”

Section: Discussionmentioning

confidence: 57%

Methylation-driven gene DLL3 is a potential prognostic biomarker in ocular melanoma correlating with metastasis

et al. 2022

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BackgroundOcular melanoma is an aggressive malignancy with a high rate of metastasis and poor prognosis. Increasing evidence indicated that DNA methylation plays an important role in the occurrence and development of ocular melanoma. Hence, exploring new diagnostic and prognostic biomarkers at the genetic level may be beneficial to the prognosis of patients with ocular melanoma.MethodsWe collected DNA methylation and gene expression profiles of human UM (uveal melanoma) and CM (conjunctival melanoma) samples from various datasets. We conducted differential methylation and expression analyses to screen the potential biomarkers. Correlation analysis was performed to investigate the relationships between the expression level of DLL3 (delta-like protein 3) and the methylation level of its corresponding CpGs. We explored the prognostic and diagnostic value of DLL3 in UM and CM. Functional annotation and GSEA (gene set enrichment analysis) were applied to get insight into the possible biological roles of DLL3. A cohort of 60 ocular melanoma patients as well as UM and CM cell lines were used to validate our findings in bioinformatic analyses.ResultsWe found that DLL3 was a methylation-driven gene correlating with UM metastasis. The CpGs of DLL3 are mainly located in the gene body and their methylation level positively correlated to DLL3 expression. Multivariate Cox regression analysis revealed that DLL3 was an independent protective factor for UM patients. High DLL3 expression significantly prolonged the overall survival and disease-free survival of UM patients. DLL3 also showed a promising power to distinguish CM from normal tissues. Functional annotation exhibited that DLL3 may suppress UM progression through modulating immune activities and down-regulating various signaling pathways. External datasets, biospecimens, and cell lines further validated the aberrant expression and prognostic role of DLL3 in ocular melanoma.ConclusionMethylation-driven gene DLL3 could serve as a new potential diagnostic and prognostic biomarker in ocular melanoma. Our findings may contribute to improving the clinical outcomes of patients with UM or CM.

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Section: Discussionmentioning

confidence: 57%

Methylation-driven gene DLL3 is a potential prognostic biomarker in ocular melanoma correlating with metastasis

et al. 2022

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“… 18 Additional mutations in the TERT promoter and ATRX may be indicate progression to melanoma. 19 , 20 TERT promoter mutations have been associated with metastatic disease in conjunctival melanoma. 19 Moreover, TERT promoter mutations have been described in PAM with moderate and severe atypia, underlining their potential as melanoma in situ lesions.…”

Section: Discussionmentioning

confidence: 99%

Bone metastasis in a case of primary acquired melanosis with atypia resulting from conjunctiva melanoma

Goemaere¹,

Lauwers²,

Keizer³

et al. 2023

American Journal of Ophthalmology Case Reports

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“…11 While recently studies have identified specific genetic mutations, such as NRAS, as contributing toward increased risk for metastasis and death, many of the tumors in this cohort were treated prior to the implementation of genetic testing, so genetic analysis was not feasible. 22 The study strengths include the large number of patients with a rare cancer in this study cohort and the comprehensive and detailed single-center data collection over a long-term period.…”

Section: Discussionmentioning

confidence: 99%

Conjunctival Melanoma in 430 Cases: Comparative Analysis of the Impact of Orbital Invasion on Tumor Recurrence, Metastasis, and Death

Baş

Dockery

Lally

et al. 2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose: To compare the clinical features at presentation and treatment outcomes of conjunctival melanoma by absence/presence of orbital invasion. Methods: A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Results: Of 430 patients with conjunctival melanoma, 21 (5%) had orbital invasion at presentation. A comparison between the 2 groups (orbital invasion absent vs. present) revealed that the orbital invasion group had a higher frequency of prior eyelid incisional biopsy (5% vs. 24%, P = 0.006), greater tumor basal diameter (12.2 vs. 17.3, P = 0.009), greater tumor thickness (2.4 vs. 7.0, P < 0.001), more quadrants involved (1.8 vs. 2.5, P = 0.002), and more clock hours involved (4.4 vs. 5.8, P = 0.037). In addition, those with orbital invasion were more likely to undergo exenteration as primary treatment (1% vs. 24%, P < 0.001). Multivariate relative risk regression analysis revealed that variables predictive of orbital invasion included greater tumor thickness (P < 0.001) and greater involvement of the fornix (P = 0.031) and tarsus (P = 0.033). Outcomes revealed orbital invasion group with greater 5-year/10-year distant metastatic rate (16%/21% vs. 63%/63%, P = 0.005), and greater melanoma-related death rate (7%/13% vs. 38%/53%, P = 0.001). Conclusions: Conjunctival melanoma with orbital invasion at presentation demonstrate larger, more extensive tumors involving the fornix or tarsus, and with greater rate of melanoma-related metastasis and death.

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Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients

Cited by 23 publications

References 47 publications

Methylation-driven gene DLL3 is a potential prognostic biomarker in ocular melanoma correlating with metastasis

Methylation-driven gene DLL3 is a potential prognostic biomarker in ocular melanoma correlating with metastasis

Bone metastasis in a case of primary acquired melanosis with atypia resulting from conjunctiva melanoma

Conjunctival Melanoma in 430 Cases: Comparative Analysis of the Impact of Orbital Invasion on Tumor Recurrence, Metastasis, and Death

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