Inactivation of the p16 cyclin-dependent kinase inhibitor in high-grade canine non-Hodgkin's T-Cell lymphoma
Inactivation of the p16 cyclin-dependent kinase inhibitor in high-grade canine non-Hodgkin's T-Cell lymphoma
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DOI：
10.1354/vp.44-4-467
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发表时间：
2007-07-01
影响因子：
2.4
通讯作者：
Modiano, J. F.
中科院分区：
文献类型：
--
作者：
Fosmire, S. P.;Thomas, R.;Modiano, J. F.
p16/Rb肿瘤抑制通路失活在t细胞非霍奇金淋巴瘤（NHL）中的意义尚不完全清楚。我们使用自然发生的犬NHL来检验p16失活具有特定病理相关性的假设。共纳入48例（22例t细胞NHL， 26例b细胞NHL）。如适用，采用中期或阵列比较基因组杂交、Southern印迹、启动子甲基化和Rb磷酸化来确定p16的存在、表达和活性。费雪精确检验用于检验显著性。p16缺失（或犬11号染色体缺失）仅限于高级别t细胞性NHL（淋巴母细胞t细胞淋巴瘤和外周t细胞淋巴瘤，未另有说明）。其特征是肿瘤细胞在典型CDK4位点Rb磷酸化的同时增加。Rb磷酸化也见于高级别b细胞NHL（弥漫性大b细胞淋巴瘤和burkitt型淋巴瘤），但在这些病例中，它似乎与c-Myc过表达有关。数据显示p16缺失或失活几乎只发生在高级别t细胞NHL中；然而，在低级别t细胞NHL和高级别b细胞NHL中，可通过其他途径产生Rb缺乏的功能性表型。根据世界卫生组织标准的形态学分类和Rb磷酸化的评估是犬NHL的预后有价值的参数。
The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p 16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based Comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.