Revealing genomic profile that underlies tropism of myeloma cells using whole exome sequencing

Abstract

Background. Previously we established two cell lines (SNU-MM1393-BM and SNU-MM1393-SC) from different tissues (bone marrow and subcutis) of mice which were injected with single patient's myeloma sample. We tried to define genetic changes specific for each cell line using whole exome sequencing (WES). Materials and Methods. We extracted DNA from SNU-MM1393-BM and SNU-MM1393-SC and performed WES. For single nucleotide variants (SNV) calling, we used Varscan2. Annotation of mutation was performed using ANNOVAR. Results. When calling of somatic mutations was performed, 68 genes were nonsynonymously mutated only in SNU-MM1393-SC, while 136 genes were nonsynonymously mutated only in SNU-MM1393-BM. KIAA1199, FRY, AP3B2, and OPTC were representative genes specifically mutated in SNU-MM1393-SC. When comparison analysis was performed using TCGA data, mutational pattern of SNU-MM1393-SC resembled that of melanoma mostly. Pathway analysis using KEGG database showed that mutated genes specific of SNU-MM1393-BM were related to differentiation, while those of SNU-MM1393-SC were related to tumorigenesis. Conclusion. We found out genetic changes that underlie tropism of myeloma cells using WES. Genetic signature of cutaneous plasmacytoma shares that of melanoma implying common mechanism for skin tropism. KIAA1199, FRY, AP3B2, and OPTC are candidate genes for skin tropism of cancers.