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Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing

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 repor...

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Autores principales: Kim, Jung-Ah, Hwang, Byungjin, Park, Si Nae, Huh, Sunghoon, Im, Kyongok, Choi, Sungbin, Chung, Hye Yoon, Huh, JooRyung, Seo, Eul-Ju, Lee, Je-Hwan, Bang, Duhee, Lee, Dong Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154520/
https://www.ncbi.nlm.nih.gov/pubmed/27959900
http://dx.doi.org/10.1371/journal.pone.0167641
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author Kim, Jung-Ah
Hwang, Byungjin
Park, Si Nae
Huh, Sunghoon
Im, Kyongok
Choi, Sungbin
Chung, Hye Yoon
Huh, JooRyung
Seo, Eul-Ju
Lee, Je-Hwan
Bang, Duhee
Lee, Dong Soon
author_facet Kim, Jung-Ah
Hwang, Byungjin
Park, Si Nae
Huh, Sunghoon
Im, Kyongok
Choi, Sungbin
Chung, Hye Yoon
Huh, JooRyung
Seo, Eul-Ju
Lee, Je-Hwan
Bang, Duhee
Lee, Dong Soon
author_sort Kim, Jung-Ah
collection PubMed
description 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.
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spelling pubmed-51545202016-12-28 Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing Kim, Jung-Ah Hwang, Byungjin Park, Si Nae Huh, Sunghoon Im, Kyongok Choi, Sungbin Chung, Hye Yoon Huh, JooRyung Seo, Eul-Ju Lee, Je-Hwan Bang, Duhee Lee, Dong Soon PLoS One Research Article 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. Public Library of Science 2016-12-13 /pmc/articles/PMC5154520/ /pubmed/27959900 http://dx.doi.org/10.1371/journal.pone.0167641 Text en © 2016 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kim, Jung-Ah
Hwang, Byungjin
Park, Si Nae
Huh, Sunghoon
Im, Kyongok
Choi, Sungbin
Chung, Hye Yoon
Huh, JooRyung
Seo, Eul-Ju
Lee, Je-Hwan
Bang, Duhee
Lee, Dong Soon
Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing
title Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing
title_full Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing
title_fullStr Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing
title_full_unstemmed Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing
title_short Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing
title_sort genomic profile of chronic lymphocytic leukemia in korea identified by targeted sequencing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154520/
https://www.ncbi.nlm.nih.gov/pubmed/27959900
http://dx.doi.org/10.1371/journal.pone.0167641
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