A complex pattern of recurrent chromosomal losses and gains in T‐cell prolymphocytic leukemia-猫眼课题宝

T 细胞幼淋巴细胞白血病中反复出现的染色体丢失和增益的复杂模式

DOI：

10.1002/gcc.1141

发表时间：

2001

期刊：

Genes

影响因子：

3.5

通讯作者：

中科院分区：

生物学3区

文献类型：

作者：

J. Soulier;G. Pierron;Danielle Vecchione;R. Garand;F. Brizard;F. Sigaux;M. Stern;A. Aurias

T细胞幼淋巴细胞白血病（T-PLL）是一种罕见的淋巴细胞恶性增殖，具有胸腺后表型。先前的细胞遗传学和分子生物学研究报道了复杂的核型，包括反复出现的染色体异常，包括涉及14q32.1的TCL 1或Xq 28的MTCP 1易位，ATM基因缺失和/或突变的失活，以及等染色体8。为了广泛研究T-PLL中的染色体不平衡，我们使用比较基因组杂交（CGH）分析了22个肿瘤DNA。在所有病例中均检测到异常CGH谱，表明高度复发性增益和损失，并在很大程度上扩展了先前确定的异常。仅观察到少数非复发性异常，与ATM失活预期的遗传不稳定性相反。在8 p处确定了9个复发性丢失区域（频率86%），11 q（68%），22 q11（45%），13 q（41%），6 q（36%），9 p（27%），12 p（23%），11 p11-p14（23%）和17 p（23%），以及在8 q（82%），14 q32（50%），22 q21-qter（41%）和6p（23%）。几个复发性染色体异常同时存在于每种情况下（平均值，5.7，高达10），没有一个是相互排斥的。荧光原位杂交分析证实并延长了22 q11和13 q的损失，最终的频率分别为55%和45%。对1例病例进行的7年分析证实了T-PLL的总体遗传稳定性，并显示肿瘤进展与少数染色体异常的发生相关。本研究建立了T-PLL中高度复发性染色体异常的复杂模式，包括一些常见于其他淋巴系统恶性肿瘤的13号染色体缺失。© 2001 Wiley利斯公司

T‐cell prolymphocytic leukemia (T‐PLL) is a rare malignant proliferation of lymphoid cells with a postthymic phenotype. Previous cytogenetic and molecular studies reported complex karyotypes with recurrent chromosomal abnormalities, including translocations involving either TCL1 at 14q32.1 or MTCP1 at Xq28, inactivation of the ATM gene by deletion and/or mutation, and isochromosomes 8. For extensive study of chromosomal imbalances in T‐PLL, we analyzed 22 tumoral DNAs using comparative genomic hybridization (CGH). Abnormal CGH profiles were detected in all cases, demonstrating highly recurrent gains and losses and largely extending the abnormalities previously established. Only a few nonrecurrent abnormalities were observed, in contrast to the genetic instability anticipated from ATM inactivation. Nine recurrent regions of loss were identified at 8p (frequency 86%), 11q (68%), 22q11 (45%), 13q (41%), 6q (36%), 9p (27%), 12p (23%), 11p11–p14 (23%), and 17p (23%), as well as four regions of gain at 8q (82%), 14q32 (50%), 22q21–qter (41%), and 6p (23%). Several recurrent chromosomal abnormalities were simultaneously present in each case (mean, 5.7; up to 10), none being mutually exclusive of another. Fluorescence in situ hybridization analysis confirmed and extended 22q11 and 13q losses, giving final frequencies of 55% and 45%, respectively. Analysis of one case over a 7‐year period confirmed the overall genetic stability of T‐PLL and showed that tumor progression was associated with the onset of a few chromosomal abnormalities. This study establishes a complex pattern of highly recurrent chromosomal abnormalities in T‐PLL, including some, such as chromosome 13 deletion, commonly found in other lymphoid malignancies. © 2001 Wiley‐Liss, Inc.

Recombinase-activating gene (RAG) 2-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice.