RT Journal
A1 Turajlic, Samra
A1 Furney, Simon J.
A1 Lambros, Maryou B.
A1 Mitsopoulos, Costas
A1 Kozarewa, Iwanka
A1 Geyer, Felipe C.
A1 MacKay, Alan
A1 Hakas, Jarle
A1 Zvelebil, Marketa
A1 Lord, Christopher J.
A1 Ashworth, Alan
A1 Thomas, Meirion
A1 Stamp, Gordon
A1 Larkin, James
A1 Reis-Filho, Jorge S.
A1 Marais, Richard
T1 Whole genome sequencing of matched primary and metastatic acral melanomas
JF Genome Research 
JO Genome Research 
YR 2011 
FD December 19 
DO 10.1101/gr.125591.111 
UL http://genome.cshlp.org/content/early/2011/12/19/gr.125591.111.abstract 
AB Next generation sequencing has enabled systematic discovery of mutational spectra in cancer samples. Here, we used whole genome sequencing to characterize somatic mutations and structural variation in a primary acral melanoma and its lymph node metastasis. Our data show that the somatic mutational rates in this acral melanoma sample pair were more comparable to the rates reported in cancer genomes not associated with mutagenic exposure than in the genome of a melanoma cell line or the transcriptome of melanoma short-term cultures. Despite the perception that acral skin is sun-protected, the dominant mutational signature in these samples is compatible with damage due to ultraviolet light exposure. A nonsense mutation in ERCC5 discovered in both the primary and metastatic tumors could also have contributed to the mutational signature through accumulation of unrepaired dipyrimidine lesions. However, evidence of transcription-coupled repair was suggested by the lower mutational rate in the transcribed regions and expressed genes. The primary and the metastasis are highly similar at the level of global gene copy number alterations, loss of heterozygosity and single nucleotide variation (SNV). Furthermore, the majority of the SNVs in the primary tumor were propagated in the metastasis and one nonsynonymous coding SNV and one splice site mutation appeared to arise de novo in the metastatic lesion.