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Distinct genetic profiles of extracranial and intracranial acral melanoma metastases
Author(s) -
Sharma Gaurav,
Lian Christine G.,
Lin William M.,
AminMansour Ali,
JanéValbuena Judit,
Garraway Levi,
Bao Wendi,
Yoon Charles H.,
Ibrahim Nageatte
Publication year - 2016
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.12746
Subject(s) - pathology , melanoma , medicine , dermatology , cancer research
Background There is limited knowledge of the genetic alterations in acral melanoma metastases at different anatomic sites. Here, we characterized the genetic abnormalities of metastases in a 51‐year‐old man with stage IIIC heel melanoma who developed concomitant brain and cutaneous metastases in spite of multiple treatment modalities. Methods Melanoma cells were isolated following palliative resection of the patient's cortical tumor and biopsy of cutaneous thigh metastasis. Mutational analysis using polymerase chain reaction amplification and BLAST, as well as exome sequencing (160 Mb coverage) was performed on the tumors, cell lines generated thereof and normal lymph nodes. Results All specimens had neuroblastoma RAS viral oncogene homolog Q61K mutations. There was a 40‐fold higher somatic mutation frequency in the brain metastasis compared to the cutaneous metastasis. The former showed truncations of DNA mismatch repair genes ( MLH1 and MSH2 ), and non‐canonical BRAF (v‐raf murine sarcoma viral oncogene homolog B1), PIK3CA and NF‐1 mutations not observed in the extracranial lesion. Genomic profiling of each cell line was concordant with the respective original tumor tissue. Conclusions We present the mutational differences between brain and cutaneous acral melanoma metastases in a patient with concomitant lesions. Further genetic and functional studies are needed to understand the biology of metastatic disease appearing at different sites.