Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that promotes tumorigenesis by epigenetic repression of tumor suppressor genes. Although EZH2 is overexpressed in many malignancies, activating EZH2 mutations have been described predominantly in follicular lymphoma and diffuse large...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-06-01
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| Series: | Human Pathology: Case Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214330014200228 |
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| author | Paul W. Harms Alexandra C. Hristov David S. Kim Tobenna Anens Michael J. Quist Javed Siddiqui Shannon Carskadon Rohit Mehra Douglas R. Fullen Timothy M. Johnson Arul M. Chinnaiyan Nallasivam Palanisamy |
| author_facet | Paul W. Harms Alexandra C. Hristov David S. Kim Tobenna Anens Michael J. Quist Javed Siddiqui Shannon Carskadon Rohit Mehra Douglas R. Fullen Timothy M. Johnson Arul M. Chinnaiyan Nallasivam Palanisamy |
| author_sort | Paul W. Harms |
| collection | DOAJ |
| description | Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that promotes tumorigenesis by epigenetic repression of tumor suppressor genes. Although EZH2 is overexpressed in many malignancies, activating EZH2 mutations have been described predominantly in follicular lymphoma and diffuse large B-cell lymphoma. EZH2 activating mutations in melanoma are not well described. Here, we report a case of cutaneous melanoma that displayed an EZH2 (Y641S) activating mutation detected by transcriptome sequencing as well as BRAF (V600K). The patient had concurrent follicular lymphoma that lacked both the EZH2 (Y641) and BRAF (V600K) mutations present in the patient's melanoma. Further, we screened publicly available sequence data and identified four additional melanoma cases harboring activating EZH2 mutation. Our findings provide additional evidence that activating recurrent EZH2 mutations occur in cutaneous melanoma, to our knowledge the first solid tumor shown to harbor such mutations. These tumors may be amenable to EZH2 inhibitor therapy. |
| first_indexed | 2024-12-23T04:05:53Z |
| format | Article |
| id | doaj.art-e9ecae430a3044439c4aa2b2925e7ff5 |
| institution | Directory Open Access Journal |
| issn | 2214-3300 |
| language | English |
| last_indexed | 2024-12-23T04:05:53Z |
| publishDate | 2014-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Human Pathology: Case Reports |
| spelling | doaj.art-e9ecae430a3044439c4aa2b2925e7ff52022-12-21T18:00:39ZengElsevierHuman Pathology: Case Reports2214-33002014-06-0112212810.1016/j.ehpc.2014.07.002Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencingPaul W. Harms0Alexandra C. Hristov1David S. Kim2Tobenna Anens3Michael J. Quist4Javed Siddiqui5Shannon Carskadon6Rohit Mehra7Douglas R. Fullen8Timothy M. Johnson9Arul M. Chinnaiyan10Nallasivam Palanisamy11Departments of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMarshfield Clinic, Marshfield, WI 54449, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USAMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartments of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAEnhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that promotes tumorigenesis by epigenetic repression of tumor suppressor genes. Although EZH2 is overexpressed in many malignancies, activating EZH2 mutations have been described predominantly in follicular lymphoma and diffuse large B-cell lymphoma. EZH2 activating mutations in melanoma are not well described. Here, we report a case of cutaneous melanoma that displayed an EZH2 (Y641S) activating mutation detected by transcriptome sequencing as well as BRAF (V600K). The patient had concurrent follicular lymphoma that lacked both the EZH2 (Y641) and BRAF (V600K) mutations present in the patient's melanoma. Further, we screened publicly available sequence data and identified four additional melanoma cases harboring activating EZH2 mutation. Our findings provide additional evidence that activating recurrent EZH2 mutations occur in cutaneous melanoma, to our knowledge the first solid tumor shown to harbor such mutations. These tumors may be amenable to EZH2 inhibitor therapy.http://www.sciencedirect.com/science/article/pii/S2214330014200228EZH2MelanomaTranscriptome sequencingLymphoma |
| spellingShingle | Paul W. Harms Alexandra C. Hristov David S. Kim Tobenna Anens Michael J. Quist Javed Siddiqui Shannon Carskadon Rohit Mehra Douglas R. Fullen Timothy M. Johnson Arul M. Chinnaiyan Nallasivam Palanisamy Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing Human Pathology: Case Reports EZH2 Melanoma Transcriptome sequencing Lymphoma |
| title | Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing |
| title_full | Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing |
| title_fullStr | Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing |
| title_full_unstemmed | Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing |
| title_short | Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing |
| title_sort | activating mutations of the oncogene ezh2 in cutaneous melanoma revealed by next generation sequencing |
| topic | EZH2 Melanoma Transcriptome sequencing Lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S2214330014200228 |
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