TY - JOUR
T1 - Melanomas of unknown primary have a mutation profile consistent with cutaneous sun-exposed melanoma
AU - Dutton-Regester, Ken
AU - Kakavand, Hojabr
AU - Aoude, Lauren G.
AU - Stark, Mitchell S.
AU - Gartside, Michael G.
AU - Johansson, Peter
AU - O'Connor, Linda
AU - Lanagan, Cathy
AU - Tembe, Varsha
AU - Pupo, Gulietta M.
AU - Haydu, Lauren E.
AU - Schmidt, Christopher W.
AU - Mann, Graham J.
AU - Thompson, John F.
AU - Scolyer, Richard A.
AU - Hayward, Nicholas K.
PY - 2013/11
Y1 - 2013/11
N2 - Summary: 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.
AB - Summary: 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.
KW - Melanoma of unknown primary
KW - Mutation profile
KW - Sequencing
UR - http://www.scopus.com/inward/record.url?scp=84886239930&partnerID=8YFLogxK
U2 - 10.1111/pcmr.12153
DO - 10.1111/pcmr.12153
M3 - Article
SN - 1755-1471
VL - 26
SP - 852
EP - 860
JO - Pigment Cell and Melanoma Research
JF - Pigment Cell and Melanoma Research
IS - 6
ER -