Mantle cell lymphoma (MCL) is derived from naïve CD5+ B-cells with the cytogenetic hallmark translocation 11;14. The presence of additional abnormalities is associated with blastoid variants in MCL (BMCL) and confers a poor prognosis. Many of these tumors also show deletion or loss of heterozygosity (LOH) of the ATM gene and biallelic ATM inactivation show significantly higher chromosomal imbalances. Here we report a 52 year-old male who presented to the clinic with worsening dyspnea, fever, chills, diffuse lymphadenopathy, splenomegaly and leukocytosis with blastoid cells circulating in blood. The bone marrow aspirate showed about 40% abnormal blast-looking cells and biopsy revealed a remarkable lymphoid infiltrate. The patient was diagnosed with blastoid variant mantle cell lymphoma (BMCL). Chromosome analysis on bone marrow showed a complex karyotype. FISH analysis from B-cell lymphoma panel showed bi-allelic amplification of ATM gene. Other abnormalities were present including CCND1/IGH fusion, confirming the MCL diagnosis, in addition to RB1 and p53 deletion. High resolution SNP-microarray studies showed complex copy number changes, especially on chromosomes 7 and 11, consistent with chromoanagenesis. Microarray studies also showed LOH at the ATM locus indicating the amplification seen on FISH is not biallelic. To the best of our knowledge, ATM gene amplification is not previously reported in BMCL and our case suggests a novel mechanism of ATM inactivation caused by chromoanagenesis resulting in mutant allele specific imbalance with copy number gain.

中文翻译：

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地幔细胞淋巴瘤的胚样变体中ATM基因的双等位基因扩增：一种由于色生成失活的新机制？

套细胞淋巴瘤（MCL）源自具有细胞遗传学标志易位的纯净CD5 + B细胞11; 14。其他异常的存在与MCL（BMCL）中的胚泡变体有关，预后不良。许多这些肿瘤还显示出ATM基因的杂合性（LOH）缺失或缺失，双等位基因ATM失活显示出明显更高的染色体失衡。在这里，我们报告了一名52岁的男性，他出现呼吸困难，发烧，发冷，弥漫性淋巴结病，脾肿大和白细胞增多，血液中有胚泡样细胞增多，就诊。骨髓抽吸物显示约40％的异常胚细胞，活检显示明显的淋巴样浸润。该患者被诊断患有胚样变体套细胞淋巴瘤（BMCL）。骨髓的染色体分析显示出复杂的核型。B细胞淋巴瘤小组的FISH分析显示ATM基因的双等位基因扩增。除RB1和p53缺失外，还存在其他异常，包括CCND1 / IGH融合，证实了MCL诊断。高分辨率SNP微阵列研究显示复杂的拷贝数变化，尤其是在7号和11号染色体上，与发色一致。微阵列研究还显示，ATM基因座处的LOH表明FISH上的扩增不是双等位基因。据我们所知，BMCL之前尚未报道过ATM基因扩增，我们的病例表明由色分析引起的ATM失活的新机制，导致突变的等位基因特异性失衡，拷贝数增加。B细胞淋巴瘤小组的FISH分析显示ATM基因的双等位基因扩增。除RB1和p53缺失外，还存在其他异常，包括CCND1 / IGH融合，证实了MCL诊断。高分辨率SNP微阵列研究显示复杂的拷贝数变化，尤其是在7号和11号染色体上，与发色一致。微阵列研究还显示，ATM基因座处的LOH表明FISH上的扩增不是双等位基因。据我们所知，BMCL之前尚未报道过ATM基因扩增，我们的病例表明由色分析引起的ATM失活的新机制，导致突变的等位基因特异性失衡，拷贝数增加。B细胞淋巴瘤小组的FISH分析显示ATM基因的双等位基因扩增。除RB1和p53缺失外，还存在其他异常，包括CCND1 / IGH融合，证实了MCL诊断。高分辨率SNP-微阵列研究显示复杂的拷贝数变化，尤其是在7号和11号染色体上，与发色一致。微阵列研究还显示，ATM基因座处的LOH表明FISH上的扩增不是双等位基因。据我们所知，BMCL以前未报道过ATM基因扩增，我们的病例表明由色分析引起的ATM失活的新机制，导致突变的等位基因特异性失衡，拷贝数增加。高分辨率SNP微阵列研究显示复杂的拷贝数变化，尤其是在7号和11号染色体上，与发色一致。微阵列研究还显示，ATM基因座处的LOH表明FISH上的扩增不是双等位基因。据我们所知，BMCL之前尚未报道过ATM基因扩增，我们的病例表明由色分析引起的ATM失活的新机制，导致突变的等位基因特异性失衡，拷贝数增加。高分辨率SNP微阵列研究显示复杂的拷贝数变化，尤其是在7号和11号染色体上，与发色一致。微阵列研究还显示，ATM基因座处的LOH表明FISH上的扩增不是双等位基因。据我们所知，BMCL之前尚未报道过ATM基因扩增，我们的病例表明由色分析引起的ATM失活的新机制，导致突变的等位基因特异性失衡，拷贝数增加。