Conjunctival melanomas harbor BRAF and NRAS mutations and copy number changes similar to cutaneous and mucosal melanomas Journal Article
| Authors: | Griewank, K. G.; Westekemper, H.; Murali, R.; Mach, M.; Schilling, B.; Wiesner, T.; Schimming, T.; Livingstone, E.; Sucker, A.; Grabellus, F.; Metz, C.; Süsskind, D.; Hillen, U.; Speicher, M. R.; Woodman, S. E.; Steuhl, K. P.; Schadendorf, D. |
| Article Title: | Conjunctival melanomas harbor BRAF and NRAS mutations and copy number changes similar to cutaneous and mucosal melanomas |
| Abstract: | Purpose: Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment options are limited and the prognosis is poor. To date, little is known of the genetic alterations in conjunctival melanomas. Experimental Design: We conducted genetic analysis of 78 conjunctival melanomas, to our knowledge the largest cohort reported to date. An oncogene hotspot array was run on 38 samples, screening for a panel of known cancer-relevant mutations. Thirty tumors were analyzed for genome-wide copy number alterations (CNA) using array-based comparative genomic hybridization. Sanger sequencing of selected target mutations was conducted in all samples. Results: BRAF mutations were identified in 23 of 78 (29%) tumors. NRAS mutations, previously not recognized as relevant in conjunctival melanoma, were detected in 14 of 78 (18%) tumors. We found CNAs affecting various chromosomes distributed across the genome in a pattern reminiscent of cutaneous and mucosal melanoma but differing markedly from uveal melanoma. Conclusions: The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma. Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents. © 2013 American Association for Cancer Research. |
| Keywords: | adult; controlled study; human tissue; aged; gene mutation; major clinical study; genetic analysis; melanoma; melanocytic nevus; uvea melanoma; comparative genomic hybridization; b raf kinase; cutaneous melanoma; oncogene braf; copy number variation; oncogene n ras; mucosal melanoma; distant metastasis free survival; conjunctiva tumor; conjunctival melanoma |
| Journal Title: | Clinical Cancer Research |
| Volume: | 19 |
| Issue: | 12 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-06-15 |
| Start Page: | 3143 |
| End Page: | 3152 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-13-0163 |
| PROVIDER: | scopus |
| PUBMED: | 23633454 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2013" - "CODEN: CCREF" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work