title: Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing.
abstract: Chronic lymphocytic leukemia (CLL) is extremely rare in Asian countries and there has been one report on genetic changes for 5 genes (TP53, SF3B1, NOTCH1, MYD88, and BIRC3) by Sanger sequencing in Chinese CLL. Yet studies of CLL in Asian countries using Next generation sequencing have not been reported. We aimed to characterize the genomic profiles of Korean CLL and to find out ethnic differences in somatic mutations with prognostic implications. We performed targeted sequencing for 87 gene panel using next-generation sequencing along with G-banding and fluorescent in situ hybridization (FISH) for chromosome 12, 13q14.3 deletion, 17p13 deletion, and 11q22 deletion. Overall, 36 out of 48 patients (75%) harbored at least one mutation and mean number of mutation per patient was 1.6 (range 0-6). Aberrant karyotypes were observed in 30.4% by G-banding and 66.7% by FISH. Most recurrent mutation (>10% frequency) was ATM (20.8%) followed by TP53 (14.6%), SF3B1 (10.4%), KLHL6 (8.3%), and BCOR (6.25%). Mutations of MYD88 was associated with moderate adverse prognosis by multiple comparisons (P = 0.055). Mutation frequencies of MYD88, SAMHD1, EGR2, DDX3X, ZMYM3, and MED12 showed similar incidence with Caucasians, while mutation frequencies of ATM, TP53, KLHL6, BCOR and CDKN2A tend to be higher in Koreans than in Caucasians. Especially, ATM mutation showed 1.5 fold higher incidence than Caucasians, while mutation frequencies of SF3B1, NOTCH1, CHD2 and POT1 tend to be lower in Koreans than in Caucasians. However, mutation frequencies between Caucasians and Koreans were not significantly different statistically, probably due to low number of patients. Collectively, mutational profile and adverse prognostic genes in Korean CLL were different from those of Caucasians, suggesting an ethnic difference, while profile of cytogenetic aberrations was similar to those of Caucasians.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung-Ah
authors.identifier: http://orcid.org/0000-0001-6934-1987
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Byungjin
authors.initials: B
authors.lastname: Hwang
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Si Nae
authors.initials: SN
authors.lastname: Park
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Huh
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyongok
authors.initials: K
authors.lastname: Im
authors.affiliation: Bachelor of Science, University of British Columbia, Vancouver, Canada.
authors.forename: Sungbin
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye Yoon
authors.initials: HY
authors.lastname: Chung
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: JooRyung
authors.initials: J
authors.lastname: Huh
authors.affiliation: Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eul-Ju
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Duhee
authors.initials: D
authors.lastname: Bang
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D007945:Leukemia, Lymphoid / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D056910:Republic of Korea; D044465:White People