Clonal heterogeneity of mantle cell lymphoma revealed by array comparative genomic hybridization

Clonal heterogeneity of mantle cell lymphoma revealed by array comparative genomic hybridization
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DOI:
10.1111/ejh.12030
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发表时间:
2013-01-01
影响因子:
3.1
通讯作者:
Seto, Masao
Seto, Masao
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Fang;Yoshida, Noriaki;Seto, Masao

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套细胞淋巴瘤 (MCL) 是一种侵袭性 B 细胞非霍奇金淋巴瘤 (NHL),其特征为 t(11;14)(q13;q32) 易位。这种淋巴瘤的预后很差,并且通过标准化疗方法仍然无法治愈。最近,我们发现大多数急性型成人 T 细胞白血病/淋巴瘤 (ATLL) 患者具有多个可能在淋巴结中产生的亚克隆。我们研究了 MCL 是否具有通过高分辨率寡阵列比较基因组杂交 (CGH) 在 ATLL 中鉴定的多个亚克隆。 20 例可评估的 MCL 病例中有 11 例 (55%) 存在 log2 比率不平衡,表明 MCL 中存在多个亚克隆。根据每个亚克隆相对于主克隆的比例,我们能够推测每个具有多个亚克隆的 MCL 病例的克隆进化。我们的分析定量、准确地为克隆异质性提供了新的见解。此外,基因组拷贝数改变不是分层事件,也不一定是细胞变成 MCL 的初始或后期事件。
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14)(q13;q32). This lymphoma exhibits a poor prognosis and remains incurable with standard chemotherapy approaches. Recently, we have shown that a majority of patients with acute-type adult T-cell leukemia/lymphoma (ATLL) have multiple subclones that were likely produced in lymph nodes. We investigated whether MCL has multiple subclones as identified in ATLL by high-resolution oligo-array comparative genomic hybridization (CGH). Eleven of 20 (55%) evaluable MCL cases had a log2 ratio imbalance, suggesting the existence of multiple subclones in MCL. Based on the proportion of every subclone relative to the main clone, we were able to speculate clonal evolution in each MCL case with multiple subclones. Our analysis gave new insights into the clonal heterogeneity quantitatively and accurately. Furthermore, genomic copy number alterations are not hierarchical events and not necessarily the initial or later events for cells to become MCL.