Melanomas of unknown primary have a mutation profile consistent with cutaneous sun-exposed melanoma

被引：52

作者：

Dutton-Regester, Ken ^{[1
]}

Kakavand, Hojabr ^{[2
]}

Aoude, Lauren G. ^{[1
]}

Stark, Mitchell S. ^{[1
]}

Gartside, Michael G. ^{[1
]}

Johansson, Peter ^{[1
]}

O'Connor, Linda ^{[3
]}

Lanagan, Cathy ^{[3
]}

Tembe, Varsha ^{[2
,4
,5
]}

Pupo, Gulietta M. ^{[2
,4
,5
]}

Haydu, Lauren E. ^{[2
,5
]}

Schmidt, Christopher W. ^{[3
]}

Mann, Graham J. ^{[2
,4
,5
]}

Thompson, John F. ^{[2
,5
,6
]}

Scolyer, Richard A. ^{[2
,5
,6
]}

Hayward, Nicholas K. ^{[1
]}

机构：

[1] QIMR Berghofer Med Res Inst, Oncogen Lab, Brisbane, Qld, Australia

[2] Melanoma Inst Australia, Sydney, NSW, Australia

[3] QIMR Berghofer Med Res Inst, Canc Immunotherapy Lab, Brisbane, Qld, Australia

[4] Westmead Millennium Inst, Westmead, NSW, Australia

[5] Univ Sydney, Sydney, NSW 2006, Australia

[6] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia

来源：

PIGMENT CELL & MELANOMA RESEARCH | 2013年 / 26卷 / 06期

基金：

英国医学研究理事会;

关键词：

melanoma of unknown primary; mutation profile; sequencing; METASTATIC MELANOMA; LYMPH-NODE; SPONTANEOUS REGRESSION; MALIGNANT-MELANOMA; SOMATIC MUTATIONS; BRAF MUTATION; WHOLE GENOME; OPEN-LABEL; DABRAFENIB; TUMOR;

D O I：

10.1111/pcmr.12153

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：852 / 860

页数：10

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