Evolution of multiple cell clones over a 29-year period of a CLL patient

被引：29

作者：

Zhao, Zhikun ^{[1
,2
,3
]}

Goldin, Lynn ^{[4
]}

Liu, Shiping ^{[1
,5
]}

Wu, Liang ^{[1
]}

Zhou, Weiyin ^{[6
]}

Lou, Hong ^{[6
]}

Yu, Qichao ^{[1
,7
]}

Tsang, Shirley X. ^{[8
]}

Jiang, Miaomiao ^{[1
,3
]}

Li, Fuqiang ^{[1
]}

McMaster, MaryLou ^{[4
]}

Li, Yang ^{[1
]}

Lin, Xinxin ^{[1
]}

Wang, Zhifeng ^{[1
]}

Xu, Liqin ^{[1
]}

Marti, Gerald ^{[9
]}

Li, Guibo ^{[1
,10
]}

Wu, Kui ^{[1
,10
]}

Yeager, Meredith ^{[6
]}

Yang, Huanming ^{[1
,11
]}

Xu, Xun ^{[1
]}

Chanock, Stephen J. ^{[4
]}

Li, Bo ^{[1
]}

Hou, Yong ^{[1
,10
]}

Caporaso, Neil ^{[4
]}

Dean, Michael ^{[1
,4
]}

机构：

[1] BGI Shenzhen, Shenzhen 518083, Peoples R China

[2] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China

[3] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing 210096, Jiangsu, Peoples R China

[4] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[5] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China

[6] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Leidos Biomed Res Inc, Bethesda, MD 20892 USA

[7] Univ Chinese Acad Sci, BGI Educ Ctr, Shenzhen 518083, Peoples R China

[8] Biomatrix, Bethesda, MD 20849 USA

[9] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA

[10] Univ Copenhagen, Dept Biol, DK-1599 Copenhagen, Denmark

[11] James D Watson Inst Genome Sci, Hangzhou 310058, Zhejiang, Peoples R China

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

美国国家卫生研究院;

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; SINGLE-CELL; EXPRESSION ANALYSIS; BIOLOGIC AGENTS; SEQUENCING DATA; R-PACKAGE; GENOME; CANCER; GENE;

D O I：

10.1038/ncomms13765

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14 -, 6q - and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death. Serial single-cell RNA sequencing reveals an expression pattern with high FOS, JUN and KLF4 at disease acceleration, which resolves following therapy, but reoccurs following relapse and death. Transcriptome evolution indicates complex changes in expression occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.

引用

页数：10

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