SEC31A-ALKFusion Gene in Lung Adenocarcinoma

김룡남,최윤라,이미숙,Maruja E. Lira,Mao Mao,Derrick Mann,Joshua Stahl,Abel Licon,최소정,Michael Van Vrancken,한종호,Iwona Wlodarska,김진국 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying patho- genesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to genera- tion of an intact, in-frame open reading frame. SEC31A-ALK encodes a predicted fusion protein of 1,438 amino acids comprising the WD40 domain of SEC31A at the N-terminus and ALK kinase domain at the C-terminus. Fluorescence in situ hybridiza- tion studies suggested that SEC31A-ALK was generated by an unbalanced genomic rearrangement associated with loss of the 3!-end of SEC31A. This is the first report of SEC31A-ALK fusion transcript in clinical NSCLC, which could be a novel diagnostic and therapeutic target for patients with NSCLC.

UbC gene allele frequency in Korean population and novel UbC mosaic repeat unit formation

김룡남,강아람,최상행,김대수,김동욱,남성혁,김애리,박건향,윤병하,이강선,박홍석 한국유전학회 2012 Genes & Genomics Vol.34 No.4

The genomic structural organization of human UbC CDS repeat units could be representative of concerted evolution. The structure of the UbC gene and its repeat unit number frequency at scales of different human ethnic populations remain to be sufficiently determined. In this study, we performed comparative analysis of UbC CDS regions in genomes from 140Korean individuals. We found that the UbC gene allele types 9, 8 and 7 are present in the Korean population in proportions of 97.1%, 0.4% and 2.5%, respectively. Interestingly, we discovered that the allele types 7 and 8 harbor the novel UbC gene mosaic repeat units 3^5 (combined between sequence parts derived from standard repeat units 3 and 5) and 8^9(combined between sequence parts derived from standard repeat units 8 and 9) within their sequence structures,respectively. Our analysis showed that the novel mosaic repeat unit 3^5 lacks the highly human-specific amino acid S38, implying a functional consequence. These results suggest that the genomic organization of UbC repeat units is still undergoing dynamic structural changes due to concerted evolution through unequal crossing-over. Our results could represent valuable data for future investigations related to treating genetic diseases caused by UbC gene mutations and variations.

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test

신희철,이한별,유태경,이은신,김룡남,박보영,윤경아,박찬이,이은숙,문형곤,노동영,공선영,한원식 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3

Purpose Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC). Materials and Methods A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017. Results Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (! 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non- BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1. Conclusion NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Comparative Analysis of Expressed Sequence Tags from the White-Rot Fungi (Phanerochaete chrysosporium)

김대원,Aeri Kim,김룡남,Seong-Hyeuk Nam,Aram Kang,Wan-Tae Chung,Sang-Haeng Choi,Hong-Seog Park 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.2

Comprehensive analysis of the transcriptome of the P. chrysosporium is a useful approach to improve our under-standing of its special and unique enzyme system and fun-gal evolution in molecular and industrial aspects. In order to unveil the functional diversity of this white-rot fungus in gene level and the expression patterns of its genes, in this study we carried out sequencing and annotation of 4,917 P. chrysosporium expressed sequence tags (ESTs). Through our bioinformatic ESTs analysis, we elucidated that 1,751 genes were derived from the present dataset of 4,917 ESTs, based on clustering and comparative genomic analyses of the ESTs. Of the 1,751 unique ESTs, 1,006 (57.5%) had homologues and orthologues in similarity searches. Our P. chrysosporium ESTs showed many genes for encoding 23 secreted proteins, many proteins for the degradation of cellulose and hemicelluloses, and heat shock proteins for stress resistance, which explain the reason why P. chryso-sporium is very important and unique white-rot fungus in dealing with contaminated resources and in degrading lig-nin and in applying this organism to several industrial as-pects. In addition, comparative analysis has shed the fresh light on the mystery about how its unique enzyme system and stress resistance have been evolved differently from its closest relatives.

TM4SF4 and LRRK2 are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis

정경수,최준석,구범모,김유진,송지영,성민정,장은솔,노가원,안성빈,이미숙,송경,이한나,김룡남,신영기,오두이,최윤라 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines. Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.