Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma

被引：88

作者：

Bouska, A. ^{[1
]}

Zhang, W. ^{[1
]}

Gong, Q. ^{[2
]}

Iqbal, J. ^{[1
]}

Scuto, A. ^{[2
]}

Vose, J. ^{[3
]}

Ludvigsen, M. ^{[4
]}

Fu, K. ^{[1
]}

Weisenburger, D. D. ^{[2
]}

Greiner, T. C. ^{[1
]}

Gascoyne, R. D. ^{[5
]}

Rosenwald, A. ^{[6
,7
]}

Ott, G. ^{[8
,9
]}

Campo, E. ^{[10
]}

Rimsza, L. M. ^{[11
]}

Delabie, J. ^{[12
]}

Jaffe, E. S. ^{[13
]}

Braziel, R. M. ^{[14
]}

Connors, J. M. ^{[15
]}

Wu, C-I ^{[16
,17
]}

Staudt, L. M. ^{[18
]}

Amore, F. D. ^{[19
]}

McKeithan, T. W. ^{[2
]}

Chan, W. C. ^{[2
]}

机构：

[1] Univ Nebraska Med Ctr, Pathol & Microbiol, Omaha, NE USA

[2] City Hope Natl Med Ctr, Dept Pathol, 1500 East Duarte Rd, Duarte, CA 91010 USA

[3] Univ Nebraska Med Ctr, Div Hematol & Oncol, Omaha, NE USA

[4] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[5] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada

[6] Univ Wurzburg, Inst Pathol, Wurzburg, Germany

[7] Comprehens Canc Ctr Mainfranken, Wurzburg, Germany

[8] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[9] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[10] Univ Barcelona, Hosp Clin, Hematopathol Unit, IDIBAPS, Barcelona, Spain

[11] Univ Arizona, Dept Pathol, Tucson, AZ USA

[12] Univ Toronto, Dept Pathol, Toronto, ON, Canada

[13] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA

[14] Oregon Hlth & Sci Univ, Portland, OR USA

[15] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC, Canada

[16] Chinese Acad Sci, Beijing Inst Genom, Beijing, Peoples R China

[17] Univ Chicago, Dept Ecol & Evolut, 940 E 57th St, Chicago, IL 60637 USA

[18] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[19] Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark

来源：

LEUKEMIA | 2017年 / 31卷 / 01期

基金：

美国国家卫生研究院;

关键词：

B-CELL LYMPHOMA; SOMATIC MUTATIONS; EZH2; MUTATIONS; CLONAL EVOLUTION; CARD11; EXPRESSION; PATHOGENESIS; SURVIVAL; FREQUENT; TARGET;

D O I：

10.1038/leu.2016.175

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Follicular lymphoma (FL) is typically an indolent disease, but 30-40% of FL cases transform into an aggressive lymphoma (tFL) with a poor prognosis. To identify the genetic changes that drive this transformation, we sequenced the exomes of 12 cases with paired FL and tFL biopsies and identified 45 recurrently mutated genes in the FL-tFL data set and 39 in the tFL cases. We selected 496 genes of potential importance in transformation and sequenced them in 23 additional tFL cases. Integration of the mutation data with copy-number abnormality (CNA) data provided complementary information. We found recurrent mutations of miR-142, which has not been previously been reported to be mutated in FL/tFL. The genes most frequently mutated in tFL included KMT2D (MLL2), CREBBP, EZH2, BCL2 and MEF2B. Many recurrently mutated genes are involved in epigenetic regulation, the Janus-activated kinase-signal transducer and activator of transcription (STAT) or the nuclear factor-kappa B pathways, immune surveillance and cell cycle regulation or are TFs involved in B-cell development. Of particular interest are mutations and CNAs affecting S1P-activated pathways through S1PR1 or S1PR2, which likely regulate lymphoma cell migration and survival outside of follicles. Our custom gene enrichment panel provides high depth of coverage for the study of clonal evolution or divergence.

引用

页码：83 / 91

页数：9

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