ATRX Loss in the Development and Prognosis of Conjunctival Melanoma
Metastatic disease is linked to <i>TERT</i> promoter mutations in conjunctival melanomas (CM). Both <i>TERT</i> promoter and <i>ATRX</i> mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in c...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12988 |
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| author | Jolique A. van Ipenburg Quincy C. C. van den Bosch Dion Paridaens Hendrikus J. Dubbink Emine Kiliç Nicole Naus Robert M. Verdijk |
| author_facet | Jolique A. van Ipenburg Quincy C. C. van den Bosch Dion Paridaens Hendrikus J. Dubbink Emine Kiliç Nicole Naus Robert M. Verdijk |
| author_sort | Jolique A. van Ipenburg |
| collection | DOAJ |
| description | Metastatic disease is linked to <i>TERT</i> promoter mutations in conjunctival melanomas (CM). Both <i>TERT</i> promoter and <i>ATRX</i> mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions. Eighty-six conjunctival melanocytic lesions from the Rotterdam Ocular Melanoma Study group were collected. <i>ATRX</i> status and <i>TERT</i> promoter status were determined using immunohistochemical staining and molecular diagnostics, respectively. None of the nevi (<i>n</i> = 16) and primary acquired melanosis (PAM) without atypia (<i>n</i> = 6) showed ATRX loss. ATRX loss was found in 2/5 PAM with atypia without CM and in 8/59 CM. No cases with a <i>TERT</i> promoter mutation (<i>n</i> = 26) showed ATRX loss. Eight/eleven metastatic CM harbored a <i>TERT</i> promoter mutation, two other metastatic CM showed ATRX loss and one metastatic case showed no <i>TERT</i> promoter/<i>ATRX</i> alterations. In conclusion ATRX loss and <i>TERT</i> promoter mutations are only found in (pre)malignant conjunctival melanocytic lesions, with most metastatic cases harboring one of these alterations, suggesting that both alterations are associated with adverse behavior. Similar to <i>TERT</i> promoter mutations, ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to having an adverse course. |
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| language | English |
| last_indexed | 2024-03-10T23:51:34Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-895e9835444b4bb29ca29a4d6add6c6a2023-11-19T01:33:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161298810.3390/ijms241612988ATRX Loss in the Development and Prognosis of Conjunctival MelanomaJolique A. van Ipenburg0Quincy C. C. van den Bosch1Dion Paridaens2Hendrikus J. Dubbink3Emine Kiliç4Nicole Naus5Robert M. Verdijk6Department of Pathology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The NetherlandsDepartment of Ophthalmology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Ophthalmology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Section Ophthalmic Pathology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Ophthalmology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Ophthalmology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Ocular Oncology, The Rotterdam Eye Hospital, Schiedamse Vest 180, 3011 BH Rotterdam, The NetherlandsMetastatic disease is linked to <i>TERT</i> promoter mutations in conjunctival melanomas (CM). Both <i>TERT</i> promoter and <i>ATRX</i> mutations are associated with faulty telomere maintenance. This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions. Eighty-six conjunctival melanocytic lesions from the Rotterdam Ocular Melanoma Study group were collected. <i>ATRX</i> status and <i>TERT</i> promoter status were determined using immunohistochemical staining and molecular diagnostics, respectively. None of the nevi (<i>n</i> = 16) and primary acquired melanosis (PAM) without atypia (<i>n</i> = 6) showed ATRX loss. ATRX loss was found in 2/5 PAM with atypia without CM and in 8/59 CM. No cases with a <i>TERT</i> promoter mutation (<i>n</i> = 26) showed ATRX loss. Eight/eleven metastatic CM harbored a <i>TERT</i> promoter mutation, two other metastatic CM showed ATRX loss and one metastatic case showed no <i>TERT</i> promoter/<i>ATRX</i> alterations. In conclusion ATRX loss and <i>TERT</i> promoter mutations are only found in (pre)malignant conjunctival melanocytic lesions, with most metastatic cases harboring one of these alterations, suggesting that both alterations are associated with adverse behavior. Similar to <i>TERT</i> promoter mutations, ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to having an adverse course.https://www.mdpi.com/1422-0067/24/16/12988conjunctival melanomageneticspathology |
| spellingShingle | Jolique A. van Ipenburg Quincy C. C. van den Bosch Dion Paridaens Hendrikus J. Dubbink Emine Kiliç Nicole Naus Robert M. Verdijk ATRX Loss in the Development and Prognosis of Conjunctival Melanoma International Journal of Molecular Sciences conjunctival melanoma genetics pathology |
| title | ATRX Loss in the Development and Prognosis of Conjunctival Melanoma |
| title_full | ATRX Loss in the Development and Prognosis of Conjunctival Melanoma |
| title_fullStr | ATRX Loss in the Development and Prognosis of Conjunctival Melanoma |
| title_full_unstemmed | ATRX Loss in the Development and Prognosis of Conjunctival Melanoma |
| title_short | ATRX Loss in the Development and Prognosis of Conjunctival Melanoma |
| title_sort | atrx loss in the development and prognosis of conjunctival melanoma |
| topic | conjunctival melanoma genetics pathology |
| url | https://www.mdpi.com/1422-0067/24/16/12988 |
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