Koh Youngil, Kim Daeyoon, Jung Woo-June, Ahn Kwang-Sung, Yoon Sung-Soo
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.
Cancer Research Institute, Seoul National University College of Medicine, Seoul 110799, Republic of Korea.
Int J Genomics. 2015;2015:675379. doi: 10.1155/2015/675379. Epub 2015 May 18.
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.
背景。此前，我们从注射了单一患者骨髓瘤样本的小鼠不同组织（骨髓和皮下组织）中建立了两个细胞系（SNU_MM1393_BM和SNU_MM1393_SC）。我们试图通过全外显子组测序（WES）来确定每个细胞系特有的基因变化。材料与方法。我们从SNU_MM1393_BM和SNU_MM1393_SC中提取DNA并进行WES。对于单核苷酸变异（SNV）的检测，我们使用了Varscan2。使用ANNOVAR对突变进行注释。结果。在进行体细胞突变检测时，68个基因仅在SNU_MM1393_SC中发生非同义突变，而136个基因仅在SNU_MM1393_BM中发生非同义突变。KIAA1199、FRY、AP3B2和OPTC是在SNU_MM1393_SC中特异性突变的代表性基因。当使用TCGA数据进行比较分析时，SNU_MM1393_SC的突变模式大多类似于黑色素瘤。使用KEGG数据库进行的通路分析表明，SNU_MM1393_BM特有的突变基因与分化相关，而SNU_MM1393_SC的突变基因与肿瘤发生相关。结论。我们通过WES发现了骨髓瘤细胞嗜性的潜在基因变化。皮肤浆细胞瘤的基因特征与黑色素瘤相同，这意味着皮肤嗜性存在共同机制。KIAA1199、FRY、AP3B2和OPTC是癌症皮肤嗜性的候选基因。
