Ning Yi, Foss Aubry, Kimball Amy S, Neill Nicholas, Matz Tricia, Schultz Roger
Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Signature Genomic Laboratories/Perkin Elmer, 2820 N Astor, Spokane, WA, 99207, USA.
Mol Cytogenet. 2013 Aug 28;6(1):34. doi: 10.1186/1755-8166-6-34.
Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement. Such cases of "double-hit" leukemia/lymphoma with both BCL2 and MYC translocations warrant further study as they are often not identified early, are associated with a poor prognosis, and are incompletely understood in molecular terms. Here we describe a patient with a diagnosis of FL that transformed to B-lymphoblastic leukemia. Detailed cytogenetic characterization of the transformed specimen using karyotype, fluorescence in situ hybridization, microarray and gene rearrangement analyses revealed a complex karyotype comprised principally of whole chromosome or whole arm copy number gains or losses. Smaller, single-gene copy number alterations identified by microarray were limited in number, but included amplification of a truncated EP300 gene and alterations in NEIL1 and GPHN. Analyses defined the presence of an IGH/BCL2 fusion due to a translocation as well as a MYC/IGH fusion due to an insertion, with both rearrangements involving the same IGH allele. The data illustrate the value in characterizing double-hit lymphoma cases with both traditional and novel technologies in the detailed cytogenetic workup.
滤泡性淋巴瘤（FL）是一种常见的非霍奇金淋巴瘤，具有转化为侵袭性更强疾病的能力，尽管很少转化为B淋巴细胞白血病/淋巴瘤。虽然t(14;18)(q32;q21)与大约90%的FL病例相关，但仅这种改变不足以导致FL，相关突变仍在阐明中。FL向B淋巴细胞白血病的转化通常包括MYC基因表达失调，典型情况是通过IGH重排。这种同时具有BCL2和MYC易位的“双打击”白血病/淋巴瘤病例值得进一步研究，因为它们往往不能早期发现，预后不良，并且在分子层面尚未完全了解。在此，我们描述了一名诊断为FL并转化为B淋巴细胞白血病的患者。使用核型分析、荧光原位杂交、微阵列和基因重排分析对转化标本进行详细的细胞遗传学特征分析，结果显示其核型复杂，主要由整条染色体或整条染色体臂的拷贝数增加或减少组成。通过微阵列鉴定出的较小的单基因拷贝数改变数量有限，但包括截短的EP300基因扩增以及NEIL1和GPHN的改变。分析确定存在因易位导致的IGH/BCL2融合以及因插入导致的MYC/IGH融合，两种重排均涉及同一个IGH等位基因。这些数据说明了在详细的细胞遗传学检查中，使用传统技术和新技术对双打击淋巴瘤病例进行特征分析的价值。
