High frequency of genetic aberrations in enteropathy-type T-cell lymphoma
High frequency of genetic aberrations in enteropathy-type T-cell lymphoma
复制标题
DOI：
10.1097/01.lab.0000090157.13040.58
复制
发表时间：
2003-10-01
影响因子：
5
通讯作者：
Starostik, P
中科院分区：
文献类型：
--
作者：
Baumgärtner, AK;Zettl, A;Starostik, P
为了确定遗传畸变在肠病型T细胞淋巴瘤（ETL）发展中的作用，我们使用一组47个微卫星标记检测了26个此类肿瘤。最常见的畸变（见40%的信息基因型）是在区域9 q34包括c-abl和Notch-1基因位点的基因组物质的扩增。在5q33.3-34和7 q31区域检测到其他频繁扩增（均超过30%）。在6p 24，7 p21，17 q23 -25，含有推定的肿瘤抑制基因的区域，以及在17p13.1的p53位点中检测到多个杂合性丢失。分析这些畸变的发生模式发现存在两个ETL亚组：其中一个的特点是9 q34畸变和另一个较小的一个显示等位基因不平衡在3q 27。这两种畸变是相互排斥的。微卫星不稳定性（MSI）检测到69%的检查淋巴瘤，MSI阳性基因型的百分比，每个肿瘤范围从2%到12%。检测到的遗传改变的频谱显示依赖于形态的模式。单态性ETL频繁显示双等位基因TCR-γ基因重排（p = 0.078，卡方（2）检验）。与多形性ETL相比，它们表现出不同的模式和更少的等位基因不平衡（没有3q 27，4 q28，13 q14，更少的5 q21或5q33.3-34畸变）和更低的MSI频率。
To define genetic aberrations playing a role in the development of enteropathy-type T-cell lymphoma (ETL), we examined 26 such tumors using a battery of 47 microsatellite markers. The most frequent aberration (seen in 40% of informative genotypes) was amplification of genomic material in region 9q34 encompassing c-abl and Notch-1 gene loci. Other frequent amplifications were detected in regions 5q33.3-34 and 7q31 (both in more than 30%). Multiple losses of heterozygosity were detected in 6p24, 7p21, 17q23-25, regions containing putative tumor suppressor genes, and in the p53 locus in 17p13.1. Analysis of the pattern of occurrence of these aberrations revealed existence of two ETL subgroups: one of them characterized by the 9q34 aberration and another smaller one showing allelic imbalances in 3q27. These two aberrations were mutually exclusive. Microsatellite instability (MSI) was detected in 69% of the examined lymphomas; the percentage of MSI-positive genotypes per tumor ranged from 2% to 12%. The spectrum of genetic alterations detected showed patterns dependent on morphology. Monomorpic ETLs displayed frequently biallelic TCR-gamma gene rearrangement (p = 0078, chi(2) test). They showed a different pattern and fewer allelic imbalances (no 3q27, 4q28, 13q14, fewer 5q21, or 5q33.3-34 aberrations) and a lower frequency of MSI than pleomorphic ETLs.