Capela de Matos Roberto R, Othman Moneeb A K, Ferreira Gerson M, Costa Elaine S, Melo Joana B, Carreira Isabel M, de Souza Mariana T, Lopes Bruno A, Emerenciano Mariana, Land Marcelo G P, Liehr Thomas, Ribeiro Raul C, Silva Maria Luiza M
Cytogenetics Department, Bone Marrow Transplantation Unit, Instituto Nacional de Câncer José de Alencar Gomes da Silva (INCA-RJ), Rio de Janeiro, Brazil; Post-Graduate Program in Oncology, Instituto Nacional de Câncer José de Alencar Gomes da Silva (INCA-RJ), Rio de Janeiro, Brazil.
Jena University Hospital, Institute of Human Genetics, Jena, Germany.
Cancer Genet. 2018 Feb;221:25-30. doi: 10.1016/j.cancergen.2017.12.002. Epub 2017 Dec 19.
Myeloid neoplasms are a heterogeneous group of hematologic disorders with divergent patterns of cell differentiation and proliferation, as well as divergent clinical courses. Rare recurrent genetic abnormalities related to this group of cancers are associated with poor outcomes. One such abnormality is the MECOM gene rearrangement that typically occurs in cases with chromosome 7 abnormalities. MECOM encodes a transcription factor that plays an essential role in cell proliferation and maintenance and also in epigenetic regulation. Aberrant expression of this gene is associated with reduced survival. Hence, its detailed characterization provides biological and clinical information relevant to the management of pediatric myeloid neoplasms. In this work, we describe a rare karyotype harboring three copies of MECOM with overexpression of the gene in a child with a very aggressive myeloid neoplasm. Cytogenetic studies defined the karyotype as 46,XX,der(7)t(3;7)(q26.2;q21.2). Array comparative genomic hybridization (aCGH) revealed a gain of 26.04 Mb in the 3q26.2-3qter region and a loss of 66.6 Mb in the 7q21.2-7qter region. RT-qPCR analysis detected elevated expression of the MECOM and CDK6 genes (458.5-fold and 35.2-fold, respectively). Overall, we show the importance of performing detailed molecular cytogenetic analysis of MECOM to enable appropriate management of high-risk pediatric myeloid neoplasms.
髓系肿瘤是一组异质性血液系统疾病，具有不同的细胞分化和增殖模式以及不同的临床病程。与这类癌症相关的罕见复发性基因异常与不良预后相关。其中一种异常是MECOM基因重排，通常发生在伴有7号染色体异常的病例中。MECOM编码一种转录因子，该转录因子在细胞增殖、维持以及表观遗传调控中发挥重要作用。该基因的异常表达与生存率降低相关。因此，对其进行详细表征可为小儿髓系肿瘤的管理提供生物学和临床信息。在这项研究中，我们描述了一名患有侵袭性很强的髓系肿瘤的儿童，其核型罕见地携带三个拷贝的MECOM且该基因过表达。细胞遗传学研究将核型确定为46,XX,der(7)t(3;7)(q26.2;q21.2)。阵列比较基因组杂交(aCGH)显示3q26.2 - 3qter区域有26.04 Mb的增益，7q21.2 - 7qter区域有66.6 Mb的缺失。RT-qPCR分析检测到MECOM和CDK6基因表达升高（分别为458.5倍和35.2倍）。总体而言，我们展示了对MECOM进行详细分子细胞遗传学分析对于合理管理高危小儿髓系肿瘤的重要性。
