Table 1.
Summary of genomic analyses performed in canine melanoma.
Table 2.
Summary of whole-genome analysis in canine melanoma discovery cohort.
Fig 1.
The mutational landscape of canine melanoma.
(A) A representative Circos plot depicting coding SNVs, CNVs, and SVs in a single mucosal melanoma. Outer circle depicts canine chromosome number. Blue triangles are SNVs located within coding regions. The middle circle denotes CNVs with gains (in red) and losses (in green) according to the aberration amplitude. Blue lines transecting the plot show translocations. (B) Numbers and types of coding mutations identified by SI-WGS and LI-WGS in the discovery cohort. *ND10-361 and ND10-363 are independent primary tumors from the same dog. (C) Integrated genomic data is presented for 34 canine melanomas and 3 canine melanoma cell lines. Each column represents data from a single tumor. Indication of tumor type (mucosal, uveal, acral, and cutaneous) is displayed above annotation of recurrently-mutated and hallmark genes. Mutations identified by WGS, aCGH, SNP array, and targeted sequencing are presented in order of frequency as are recurrent CNV regions identified by SNP array and GISTIC as well as recurrent regions involved in translocations identified by LI-WGS. Genomic analysis annotation, tumor ID, and figure legend are presented at the bottom of the figure.
Fig 2.
Recurrent somatic alterations in canine melanoma.
(A) Distribution of RAS mutations within the cohort of 37 samples (n = 9). (B) Recurrently amplified region of CFA10 found in nine tumors, which is defined by the minimal region surrounding MDM2. (C) Location of potentially deleterious mutations present in the putative tumor suppressor PTPRJ found through Sanger sequencing of the coding sequence of each tumor. (D) Individual mutations and their locations within TP53.
Fig 3.
Key deregulated pathways in canine and human melanoma.
(A) Mutation rate in canine and human melanoma subtypes is shown as somatic SNVs per DNA Mb based on WGS in our discovery cohort compared to WGS data from 140 human cutaneous, 35 acral, and 8 mucosal melanomas (Hayward et al., 2017). CM = Canine mucosal, HA = Human acral, HM = Human mucosal, and HC = Human cutaneous melanoma. Orange and blue dots in the CM plot represent the individual acral and cutaneous subtypes, respectively, in our discovery cohort. (B) Fraction of copy-number-altered genome in canine melanoma and human melanoma sequencing cohorts. (C) Total number of structural variants identified in canine and human melanoma sequencing cohorts. (D) Comparison of C>T transitions in the major melanoma types in dipyrimidine versus non-dipyrimidines. (E) Overall frequency of mutations in key melanoma pathways in our full cohort of 31 mucosal tumors compared to WGS in other subtypes from Hayward et al., 2017.