Deleeuw Ronald J, Zettl Andreas, Klinker Erdwine, Haralambieva Eugenia, Trottier Magan, Chari Raj, Ge Yong, Gascoyne Randy D, Chott Andreas, Müller-Hermelink Hans-Konrad, Lam Wan L
Department of Cancer Genetics, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
Gastroenterology. 2007 May;132(5):1902-11. doi: 10.1053/j.gastro.2007.03.036. Epub 2007 Mar 24.
BACKGROUND & AIMS: Enteropathy-type T-cell lymphoma (ETL) is an aggressive extranodal T-cell non-Hodgkin lymphoma assumed to arise in the setting of celiac disease.
To precisely define the genetic alterations underlying the pathogenesis of ETL, 30 ETL samples were profiled for genetic copy number alterations using high-resolution whole-genome tiling path array comparative genomic hybridization. To investigate the potential association of genetic alterations in ETL with celiac disease, HLA-DQB1 genotyping was performed.
By array comparative genomic hybridization, 13 novel recurrent minimal regions of chromosomal alteration were identified on multiple chromosome arms. ETL is characterized by frequent complex gains of 9q31.3-qter (70% of cases), or by an almost mutually exclusive 2.5-megabase loss of 16q12.1 (23% of cases). Two distinct groups of ETL could be delineated morphologically and genetically: type 1 ETL is characterized by nonmonomorphic cytomorphology, CD56 negativity, and chromosomal gains of 1q and 5q. Type 1 ETL also appears to be linked pathogenetically to celiac disease, sharing genetic alterations and HLA-DQB1 genotype patterns with (refractory) celiac disease. Type 2 ETL shows monomorphic small- to medium-sized tumor cell morphology, frequently shows CD56 expression, MYC oncogene locus gain, and rare gains of chromosomes 1q and 5q. In contrast to type 1 ETL, type 2 ETL shows a HLA-DQB1 genotype pattern more resembling that of the normal Caucasian population.
Contrary to current clinical classification, ETL comprises 2 morphologically, clinically, and genetically distinct lymphoma entities. In addition, type 2 ETL may not be associated with celiac disease.
肠病型T细胞淋巴瘤（ETL）是一种侵袭性结外T细胞非霍奇金淋巴瘤，被认为起源于乳糜泻背景。
为精确确定ETL发病机制的基因改变，使用高分辨率全基因组平铺路径阵列比较基因组杂交技术对30例ETL样本进行基因拷贝数改变分析。为研究ETL基因改变与乳糜泻的潜在关联，进行了HLA - DQB1基因分型。
通过阵列比较基因组杂交，在多个染色体臂上鉴定出13个新的复发性最小染色体改变区域。ETL的特征是9q31.3 - qter频繁复杂增加（70%的病例），或几乎相互排斥的16q12.1 2.5兆碱基缺失（23%的病例）。ETL可在形态和基因上分为两个不同的组：1型ETL的特征是非单形性细胞形态、CD56阴性以及1q和5q染色体增加。1型ETL在发病机制上似乎也与乳糜泻有关，与（难治性）乳糜泻共享基因改变和HLA - DQB1基因型模式。2型ETL表现为单形性中小肿瘤细胞形态，常表现CD56表达、MYC癌基因位点增加以及1q和5q染色体罕见增加。与1型ETL相反，2型ETL的HLA - DQB1基因型模式更类似于正常白种人群。
与当前临床分类相反，ETL包括两个在形态、临床和基因上不同的淋巴瘤实体。此外，2型ETL可能与乳糜泻无关。
