Fig 1.
Pedigrees of the five melanoma-prone families.
Tumor types are described beneath each individual, followed by the age of onset. Small black arrow indicates the index case of each family. The green arrow indicates the individuals who were subjected to WES analysis.
Table 1.
Clinical characteristics of cutaneous melanoma patients.
Table 2.
Clinical characteristics of melanoma patients.
Fig 2.
Diagram of the germline sequencing analysis and variant prioritization strategy, showing the main technical processes.
WES data from 10 melanoma patients were analyzed using quality and frequency-based filters, resulting in 288 rare non-synonymous variants identified in both affected members of each family, which were investigated further for their predicted pathogenicity and gene function. WES, whole exome sequencing. TMAP, Torrent Mapper; TVC, Torrent Variant Caller; GATK, Genomic Analysis Toolkit; QC, Quality Control; MAF, minor allele frequency; LoF, Loss of Function.
Table 3.
Types of rare non-synonymous heterozygous variants co-segregating in both affected relatives of the five melanoma-prone families.
Table 4.
Rare germline LoF variants identified by WES in the 5 melanoma-prone families.
Table 5.
Detected genes associated with the phenotypes of interest and their respective rare non-synonymous variants.
Fig 3.
Network of 13 genes harboring rare germline variants identified in melanoma-prone patients.
Network generated by the IPA software displaying interactions between 13 genes identified by exome sequencing and 22 other genes automatically included after they were identified as biologically connected based on scientific evidence. The functional categorization of this network was cancer, dermatological diseases, and organismal injuries and abnormalities. The red nodes represent genes identified by this study harboring missense variants; the green nodes represent genes identified harboring LoF variants; the white node genes were plotted by the software once they are associated by scientific evidence. The nodes highlighted in pink represent genes involved in melanoma tumorigenesis according to IPA.
Table 6.
Main cellular function and diseases associated with 91 prioritized genes.