Department of Pathology, University Hospital Brno, 625 00 Brno, Czech Republic.
Int J Oncol. 2010 Mar;36(3):699-706. doi: 10.3892/ijo_00000545.
Mantle cell lymphoma (MCL) is typified by translocation t(11;14)(q13;q32) causing upregulation of cyclin D1 and deregulation of cell cycle. The cyclin D1 activation plays a critical role in MCL pathogenesis but additional oncogenic events, such as aberrations of the ARF/MDM2/p53 pathway are also necessary for progression of the disease. We analyzed the p53 tumor suppressor in tumor tissue of 33 patients with MCL. The p53 status was determined by functional analyses in yeast (FASAY) and by cDNA sequencing. The level of the p53 protein was assessed by immunohistochemistry and immunoblotting. Loss of the p53-specific locus 17p13.3 was detected by FISH. Mutations in the p53 gene were detected in nine samples and they included eight missense mutations and one short deletion causing frame shift and premature stop codon formation in position 169. This mutation was associated with mRNA decay as revealed by sequencing of the p53 gDNA. All eight missense mutations were manifested by accumulation of the p53 protein in nuclei of tumor cells and three of them exhibited loss of the p53-specific locus 17p13.3. The p53 mutations were shown to be a negative prognostic marker in MCL.
套细胞淋巴瘤（MCL）的特征是易位 t(11;14)(q13;q32)，导致 cyclin D1 上调和细胞周期失调。cyclin D1 的激活在 MCL 的发病机制中起着关键作用，但额外的致癌事件，如 ARF/MDM2/p53 通路的异常，也是疾病进展所必需的。我们分析了 33 例 MCL 肿瘤组织中的抑癌基因 p53。通过酵母（FASAY）功能分析和 cDNA 测序确定 p53 状态。通过免疫组化和免疫印迹法评估 p53 蛋白水平。通过 FISH 检测 p53 特异性基因座 17p13.3 的缺失。在九个样本中检测到 p53 基因突变，包括 8 个错义突变和一个短缺失，导致 169 位的移码和提前终止密码子形成。这一突变与 p53 gDNA 测序显示的 mRNA 衰减有关。所有 8 个错义突变都表现为肿瘤细胞核中 p53 蛋白的积累，其中 3 个显示出 p53 特异性基因座 17p13.3 的缺失。p53 突变被证明是 MCL 的一个负预后标志物。
