title: 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.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul 110744, Republic of Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110799, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 110744, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul 110799, Republic of Korea.
authors.forename: Daeyoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul 110799, Republic of Korea.
authors.forename: Woo-June
authors.initials: WJ
authors.lastname: Jung
authors.affiliation: Functional Genome Institute, PDXen Biosystem Inc., Seoul 143901, Republic of Korea.
authors.forename: Kwang-Sung
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul 110744, Republic of Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110799, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 110744, Republic of Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon