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Koh, Youngil,Jung, Woo-June,Ahn, Kwang-Sung,Yoon, Sung-Soo Hindawi Publishing Corporation 2014 BioMed research international Vol.2014 No.-
<P><I>Purpose.</I> We tried to establish clinically relevant human myeloma cell lines that can contribute to the understanding of multiple myeloma (MM). <I>Materials and Methods.</I> Mononuclear cells obtained from MM patient's bone marrow were injected via tail vein in an NRG/SCID mouse. Fourteen weeks after the injection, tumor developed at subcutis of the mouse. The engraftment of MM cells into mouse bone marrow (BM) was also observed. We separated and cultured cells from subcutis and BM. <I>Results.</I> After the separation and culture of cells from subcutis and BM, we established two cell lines originating from a single patient (SNU_MM1393_BM and SNU_MM1393_SC). Karyotype of the two newly established MM cell lines showed tetraploidy which is different from the karyotype of the patient (diploidy) indicating clonal evolution. In contrast to SNU_MM1393_BM, cell proliferation of SNU_MM1393_SC was IL-6 independent. SNU_MM1393_BM and SNU_MM1393_SC showed high degree of resistance against bortezomib compared to U266 cell line. SNU_MM1393_BM had the greater lethality compared to SNU_MM1393_SC. <I>Conclusion.</I> Two cell lines harboring different site tropisms established from a single patient showed differences in cytokine response and lethality. Our newly established cell lines could be used as a tool to understand the biology of multiple myeloma.</P>
( Youngil Koh ),( Hyun Jung Lee ),( Kwang Sung Ahn ),( Young Wook Kim ),( Jong Sun Jung ),( Hyung Lae Kim ),( Jung Whan Yook ),( Hyun Kyung Park ),( Keunchil Park ),( Sung Soo Yoon ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1
Background: Current cancer research using massive parallel sequencing technologies primarily focuses on somatic changes in the cancer genome. However, it is anticipated that individual germline variations might contribute to tumorigenesis, as exemplified by several well-known examples, such as BRCA2 variations in breast cancer. Thus, it is also important to explore crosstalk between germline variation and somatic mutation in cancer. Methods: We performed whole-exome sequencing (WES) of 80 acute myeloid leukemia (AML) samples and 180 non-small cell lung cancer (NSCLC) samples. First, we searched for cancer hotspots in germline DNA of these samples. Also, we called somatic variants using in-house pipeline Adiscan. Germline hotspot alteration was validated in a separate AML cohort. Results: Non-synonymous changes including MLH1 (Chr3;37067240, T>A), KIT (Chr4;55593464, A>T), and MET (Chr 7;116340262, A>C) were observed in germline of both AML and NSCLC patients. MLH1 germline change was not found in 18 healthy control samples. Frequency of MLH1, KIT, and MET germline changes were similar in AML and NSCLC patients. In contrast to AML, some of NSCLC patients had PTEN, TP53 and STK11 germline changes. When we focused on the crosstalk between germline change and somatic mutation, MET germline alteration seemed to have coupling with IDH2 somatic mutation, while MLH1 germline mutation seemd to have coupling with TTN somatic mutation. When validated in a separate cohort, AML patients with MET germline mutation had good prognosis compred to MET wild-types suggesting prognostic impact of MET germline alteration. Conclusions: Cancer hotspot variations are present in germline of cancer patients, and their frequency might be different across various cancer subtypes. Germline alteration per se may have prognostic impact, and coupling between certain germline alteration and somatic mutation would exist.
Case Reports : Lactic acidosis associated with the usual theophylline dose in a patient with asthma
Youngil I. Koh,Inseon S. Choi 대한내과학회 2002 The Korean Journal of Internal Medicine Vol.17 No.2
Metabolic and electrolyte abnormalities, including hypokalemia, hyperglycemia and lactic acidosis, are associated with theophylline overdose. However, we report an unusual case of sinus tachycardia, lactic acidosis, hypokalemia and hyperglycemia associated
Genomics of diffuse large B cell lymphoma
Youngil Koh 대한혈액학회 2021 Blood Research Vol.56 No.-
Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.