Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine
Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation seq...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/15/3836 |
| id |
doaj-08deec0bb49743e5aad98e99e5a3585e |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Sophie Gardrat Alexandre Houy Kelly Brooks Nathalie Cassoux Raymond Barnhill Stéphane Dayot Ivan Bièche Virginie Raynal Sylvain Baulande Richard Marais Sergio Roman-Roman Marc-Henri Stern Manuel Rodrigues |
| spellingShingle |
Sophie Gardrat Alexandre Houy Kelly Brooks Nathalie Cassoux Raymond Barnhill Stéphane Dayot Ivan Bièche Virginie Raynal Sylvain Baulande Richard Marais Sergio Roman-Roman Marc-Henri Stern Manuel Rodrigues Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine Cancers conjunctival melanoma sun exposure nevus primary acquired melanocytosis <i>BRAF</i> <i>NRAS</i> |
| author_facet |
Sophie Gardrat Alexandre Houy Kelly Brooks Nathalie Cassoux Raymond Barnhill Stéphane Dayot Ivan Bièche Virginie Raynal Sylvain Baulande Richard Marais Sergio Roman-Roman Marc-Henri Stern Manuel Rodrigues |
| author_sort |
Sophie Gardrat |
| title |
Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine |
| title_short |
Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine |
| title_full |
Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine |
| title_fullStr |
Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine |
| title_full_unstemmed |
Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine |
| title_sort |
definition of biologically distinct groups of conjunctival melanomas according to etiological factors and implications for precision medicine |
| publisher |
MDPI AG |
| series |
Cancers |
| issn |
2072-6694 |
| publishDate |
2021-07-01 |
| description |
Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation sequencing of 400 genes. Hotspot mutations in <i>BRAF</i>, <i>NRAS</i>, <i>HRAS</i>, and <i>KIT</i> were observed in 16 (34%), 5 (11%), 2, and 2 cases, respectively. Patients with <i>BRAF</i> and <i>CDKN2A</i>-mutated ConjMel tended to be younger while the <i>NF1</i>-mutated one tended to be older. The eight tumors arising from nevi were enriched in <i>CTNNB1</i> mutations (63% vs. 8%; Fisher’s exact <i>p</i>-test = 0.001) compared to non-nevi ConjMel and five were devoid of <i>BRAF</i>, <i>RAS</i>, <i>NF1</i>, or <i>KIT</i> mutations, suggesting a specific oncogenic process in these tumors. The two <i>KIT</i>-mutated cases carried <i>SF3B1</i> mutations and were located on sun-protected mucosa, a genotype shared with genital and anorectal mucosal melanomas. Targetable mutations were observed in <i>ERBB2</i>, <i>IDH1</i>, <i>MET</i>, and <i>MAP2K1</i> (one occurrence each). Mutational landscape of ConjMel characterizes distinct molecular subtypes with oncogenic drivers common with mucosal and skin melanomas. <i>CTNNB1</i> mutations were associated with nevus-derived ConjMel. Concomitant <i>KIT</i>/<i>SF3B1</i> mutations in sun-protected cases suggest a common tumorigenic process with genital and anorectal mucosal melanomas. |
| topic |
conjunctival melanoma sun exposure nevus primary acquired melanocytosis <i>BRAF</i> <i>NRAS</i> |
| url |
https://www.mdpi.com/2072-6694/13/15/3836 |
| work_keys_str_mv |
AT sophiegardrat definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT alexandrehouy definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT kellybrooks definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT nathaliecassoux definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT raymondbarnhill definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT stephanedayot definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT ivanbieche definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT virginieraynal definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT sylvainbaulande definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT richardmarais definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT sergioromanroman definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT marchenristern definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine AT manuelrodrigues definitionofbiologicallydistinctgroupsofconjunctivalmelanomasaccordingtoetiologicalfactorsandimplicationsforprecisionmedicine |
| _version_ |
1721218772785692672 |
| spelling |
doaj-08deec0bb49743e5aad98e99e5a3585e2021-08-06T15:20:39ZengMDPI AGCancers2072-66942021-07-01133836383610.3390/cancers13153836Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision MedicineSophie Gardrat0Alexandre Houy1Kelly Brooks2Nathalie Cassoux3Raymond Barnhill4Stéphane Dayot5Ivan Bièche6Virginie Raynal7Sylvain Baulande8Richard Marais9Sergio Roman-Roman10Marc-Henri Stern11Manuel Rodrigues12INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer and PSL Research University, Department of Biopathology, Institut Curie, PSL Research University, F-75005 Paris, FranceINSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, F-75005 Paris, FranceMolecular Oncology Group, CRUK Manchester Institute, The University of Manchester, Alderley Park, Manchester M13 9PL, UKDepartment of Ocular Oncology, Faculty of Medicine, Institut Curie, Université de Paris Descartes, F-75005 Paris, FranceDepartment of Biopathology, Institut Curie, PSL Research University, F-75005 Paris, FranceINSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, F-75005 Paris, FranceINSERM U1016, Institut Curie, Department of Genetics, Faculty of Pharmaceutical and Biological Sciences, Université de Paris, F-75005 Paris, FranceInstitut Curie Genomics of Excellence (ICGex) Platform, Institut Curie, PSL Research University, F-75005 Paris, FranceInstitut Curie Genomics of Excellence (ICGex) Platform, Institut Curie, PSL Research University, F-75005 Paris, FranceMolecular Oncology Group, CRUK Manchester Institute, The University of Manchester, Alderley Park, Manchester M13 9PL, UKTranslational Research Department, Institut Curie, PSL Research University, F-75005 Paris, FranceINSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, F-75005 Paris, FranceINSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, F-75005 Paris, FranceConjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation sequencing of 400 genes. Hotspot mutations in <i>BRAF</i>, <i>NRAS</i>, <i>HRAS</i>, and <i>KIT</i> were observed in 16 (34%), 5 (11%), 2, and 2 cases, respectively. Patients with <i>BRAF</i> and <i>CDKN2A</i>-mutated ConjMel tended to be younger while the <i>NF1</i>-mutated one tended to be older. The eight tumors arising from nevi were enriched in <i>CTNNB1</i> mutations (63% vs. 8%; Fisher’s exact <i>p</i>-test = 0.001) compared to non-nevi ConjMel and five were devoid of <i>BRAF</i>, <i>RAS</i>, <i>NF1</i>, or <i>KIT</i> mutations, suggesting a specific oncogenic process in these tumors. The two <i>KIT</i>-mutated cases carried <i>SF3B1</i> mutations and were located on sun-protected mucosa, a genotype shared with genital and anorectal mucosal melanomas. Targetable mutations were observed in <i>ERBB2</i>, <i>IDH1</i>, <i>MET</i>, and <i>MAP2K1</i> (one occurrence each). Mutational landscape of ConjMel characterizes distinct molecular subtypes with oncogenic drivers common with mucosal and skin melanomas. <i>CTNNB1</i> mutations were associated with nevus-derived ConjMel. Concomitant <i>KIT</i>/<i>SF3B1</i> mutations in sun-protected cases suggest a common tumorigenic process with genital and anorectal mucosal melanomas.https://www.mdpi.com/2072-6694/13/15/3836conjunctival melanomasun exposurenevusprimary acquired melanocytosis<i>BRAF</i><i>NRAS</i> |