Melanomas of unknown primary have a mutation profile consistent with cutaneous sun‐exposed melanoma |
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| Authors: | Ken Dutton‐Regester Hojabr Kakavand Lauren G Aoude Mitchell S Stark Michael G Gartside Peter Johansson Linda O'Connor Cathy Lanagan Varsha Tembe Gulietta M Pupo Lauren E Haydu Christopher W Schmidt Graham J Mann John F Thompson Richard A Scolyer Nicholas K Hayward |
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| Institution: | 1. Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, , Brisbane, QLD, Australia;2. Melanoma Institute of Australia (formerly the Sydney Melanoma Unit), , North Sydney, NSW, Australia;3. Cancer Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, , Brisbane, QLD, Australia;4. Westmead Millennium Institute, , Westmead, NSW, Australia;5. The University of Sydney, , Sydney, NSW, Australia;6. Royal Prince Alfred Hospital, , Camperdown, NSW, Australia |
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| Abstract: | Melanoma of unknown primary (MUP) is an uncommon phenomenon whereby patients present with metastatic disease without an evident primary site. To determine their likely site of origin, we combined exome sequencing from 33 MUPs to assess the total rate of somatic mutations and degree of UV mutagenesis. An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11. Results showed that the majority of MUPs exhibited high somatic mutation rates, high ratios of C>T/G>A transitions, and a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun‐exposed melanomas. These data suggest that a significant proportion of MUPs arise from regressed or unrecognized primary cutaneous melanomas or arise de novo in lymph nodes from nevus cells that have migrated from the skin. |
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| Keywords: | melanoma of unknown primary mutation profile sequencing |
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