Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi
Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be...
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MDPI AG
2019-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/4/546 |
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| author | Philipp Jansen Ioana Cosgarea Rajmohan Murali Inga Möller Antje Sucker Cindy Franklin Annette Paschen Anne Zaremba Titus J. Brinker Ingo Stoffels Dirk Schadendorf Joachim Klode Eva Hadaschik Klaus G. Griewank |
| author_facet | Philipp Jansen Ioana Cosgarea Rajmohan Murali Inga Möller Antje Sucker Cindy Franklin Annette Paschen Anne Zaremba Titus J. Brinker Ingo Stoffels Dirk Schadendorf Joachim Klode Eva Hadaschik Klaus G. Griewank |
| author_sort | Philipp Jansen |
| collection | DOAJ |
| description | Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including <i>n</i> = 87 (67%) <i>BRAF</i>, <i>n</i> = 24 (18%) <i>NRAS</i>, and one (1%) <i>MAP2K1</i> mutations. <i>BRAF</i> mutations were almost exclusively V600E (<i>n</i> = 86, 99%) and primarily found in junctional and compound naevi. <i>NRAS</i> mutations were either Q61K or Q61R and frequently identified in dermal naevi. Recurrent non-V600E <i>BRAF</i>, <i>KIT</i>, <i>NF1</i>, and <i>TERT</i> promoter mutations, present in acral melanoma, were not identified. Our study identifies <i>BRAF</i> and <i>NRAS</i> mutations as the primary pathogenic event in acral naevi, however, distributed differently to those in non-acral naevi. The mutational profile of acral naevi is distinct from acral melanoma, which may be of diagnostic value in distinguishing these entities. |
| first_indexed | 2024-03-12T07:08:02Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:08:02Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5033799987784e52b0e52b39a02d5af32023-09-02T23:17:37ZengMDPI AGCancers2072-66942019-04-0111454610.3390/cancers11040546cancers11040546Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral NaeviPhilipp Jansen0Ioana Cosgarea1Rajmohan Murali2Inga Möller3Antje Sucker4Cindy Franklin5Annette Paschen6Anne Zaremba7Titus J. Brinker8Ingo Stoffels9Dirk Schadendorf10Joachim Klode11Eva Hadaschik12Klaus G. Griewank13Department of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UKDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, University of Cologne, 50937 Cologne, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen, 45147 Essen, GermanyAcral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including <i>n</i> = 87 (67%) <i>BRAF</i>, <i>n</i> = 24 (18%) <i>NRAS</i>, and one (1%) <i>MAP2K1</i> mutations. <i>BRAF</i> mutations were almost exclusively V600E (<i>n</i> = 86, 99%) and primarily found in junctional and compound naevi. <i>NRAS</i> mutations were either Q61K or Q61R and frequently identified in dermal naevi. Recurrent non-V600E <i>BRAF</i>, <i>KIT</i>, <i>NF1</i>, and <i>TERT</i> promoter mutations, present in acral melanoma, were not identified. Our study identifies <i>BRAF</i> and <i>NRAS</i> mutations as the primary pathogenic event in acral naevi, however, distributed differently to those in non-acral naevi. The mutational profile of acral naevi is distinct from acral melanoma, which may be of diagnostic value in distinguishing these entities.https://www.mdpi.com/2072-6694/11/4/546acralnaevimelanomageneticsdermatology |
| spellingShingle | Philipp Jansen Ioana Cosgarea Rajmohan Murali Inga Möller Antje Sucker Cindy Franklin Annette Paschen Anne Zaremba Titus J. Brinker Ingo Stoffels Dirk Schadendorf Joachim Klode Eva Hadaschik Klaus G. Griewank Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi Cancers acral naevi melanoma genetics dermatology |
| title | Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi |
| title_full | Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi |
| title_fullStr | Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi |
| title_full_unstemmed | Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi |
| title_short | Frequent Occurrence of <i>NRAS</i> and <i>BRAF</i> Mutations in Human Acral Naevi |
| title_sort | frequent occurrence of i nras i and i braf i mutations in human acral naevi |
| topic | acral naevi melanoma genetics dermatology |
| url | https://www.mdpi.com/2072-6694/11/4/546 |
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