Increasing genomic and epigenomic complexity in the clonal evolution from in situ to manifest t(14;18)-positive follicular lymphoma

被引：51

作者：

Schmidt, J. ^{[1
,2
]}

Salaverria, I. ^{[3
]}

Haake, A. ^{[3
]}

Bonzheim, I. ^{[1
,2
]}

Adam, P. ^{[1
,2
]}

Montes-Moreno, S. ^{[4
]}

Piris, M. A. ^{[4
]}

Fend, F. ^{[1
,2
]}

Siebert, R. ^{[3
]}

Quintanilla-Martinez, L. ^{[1
,2
]}

机构：

[1] Univ Tubingen, Inst Pathol, D-72076 Tubingen, Germany

[2] Univ Tubingen, Ctr Comprehens Canc, D-72076 Tubingen, Germany

[3] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany

[4] Hosp Univ Marques de Valdecilla, Inst Formac & Invest Marques de Valdecilla, Dept Pathol, Santander, Spain

来源：

LEUKEMIA | 2014年 / 28卷 / 05期

关键词：

genetic alterations; Follicular lymphoma in situ; CGH; POLYMERASE-CHAIN-REACTION; B-CELL LYMPHOMAS; SOMATIC MUTATIONS; HODGKIN-LYMPHOMA; DNA METHYLATION; EZH2; MUTATIONS; TRANSLOCATION; BLOOD; GENE; HYBRIDIZATION;

D O I：

10.1038/leu.2013.307

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Follicular lymphoma (FL) is characterized besides the t(14; 18)(q32; q21), by recurrent chromosomal alterations and somatic mutations. In this study, we analyzed cases of FL in situ (FLIS) without manifest FL (mFL), partial involvement by FL (PFL) and paired cases of FLIS and mFL to detect possible early chromosomal imbalances, mutations, as well as DNA-methylation patterns of genomic regions of selected genes. We demonstrate that all paired FLIS and mFL cases were clonally related, based on IGH rearrangement patterns and BCL2 breakpoint sequences. FLIS and PFL had no or few secondary chromosomal imbalances detectable by array comparative genomic hybridization (FLIS 0.8 copy number alterations (CNA)/case; PFL 2.0 CNA/case; mFL 6.3 CNA/case) and a lower level of DNA methylation of genes recurrently de novo methylated in lymphomas, as compared with mFL. EZH2 Tyr641 mutations were detected in a subset of both FLIS (2/9) and PFL (1/3) cases. In conclusion, these findings provide evidence that FLIS represents a FL precursor lesion of long-lived clonal B cells carrying the t(14; 18) with no or few secondary genetic changes. Our data suggest that there may be more than one distinct lesion driving the progression from FLIS to manifest lymphoma.

引用

页码：1103 / 1112

页数：10

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