La Starza Roberta, Barba Gianluca, Nofrini Valeria, Pierini Tiziana, Pierini Valentina, Marcomigni Luca, Perruccio Katia, Matteucci Caterina, Storlazzi Clelia Tiziana, Daniele Giulia, Crescenzi Barbara, Giansanti Michele, Giovenali Paolo, Dal Cin Paola, Mecucci Cristina
Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy.
Oncology Unit, General Hospital, Perugia, Italy.
Cancer Genet. 2013 Nov;206(11):387-92. doi: 10.1016/j.cancergen.2013.10.005. Epub 2013 Nov 4.
To provide new insights into the genomic profile of desmoplastic round cell tumors (DSRCT), we applied fluorescence in situ hybridization (FISH) and metaphase comparative genomic hybridization (M-CGH) to two newly diagnosed cases. FISH detected multiple subclones bearing one to three copies of der(11)t(11;22)(p13;q12) and/or der(22)t(11;22)(p13;q12) in both patients. This peculiar genomic imbalance might result from derivative chromosome duplication due to non-disjunction and/or mitotic recombination between normal and derivative chromosomes 11 and 22. Concomitant loss of normal chromosomes (i.e., 11 in patient 1 and 22 in patient 2) caused loss of the WT1 or EWSR1 wild-type allele. M-CGH identified other genomic imbalances: gain at chromosome 3 in both cases and chromosome 5 polysomy in patient 1. Common genomic events (i.e., trisomy 3 and extra EWSR1-WT1 and WT1-EWSR1 copies) probably contributed to disease pathogenesis and/or evolution of DSRCT. Our study demonstrated that an integrated molecular cytogenetic approach identified EWSR1-WT1 cooperating molecular events and genetic markers for prognosis. Thus, FISH and M-CGH might well be applied in a large series of patients to elucidate the genomic background of DSRCT.
为了深入了解促结缔组织增生性小圆细胞肿瘤（DSRCT）的基因组特征，我们对两例新诊断的病例应用了荧光原位杂交（FISH）和中期比较基因组杂交（M-CGH）技术。FISH检测到两名患者中均存在多个亚克隆，这些亚克隆携带1至3份der(11)t(11;22)(p13;q12)和/或der(22)t(11;22)(p13;q12)拷贝。这种特殊的基因组失衡可能是由于正常与衍生的11号和22号染色体之间的不分离和/或有丝分裂重组导致衍生染色体复制所致。正常染色体的伴随性缺失（即患者1中的11号染色体和患者2中的22号染色体）导致WT1或EWSR1野生型等位基因缺失。M-CGH鉴定出其他基因组失衡：两例均存在3号染色体增益，患者1存在5号染色体多体性。常见的基因组事件（即3号染色体三体以及额外的EWSR1-WT1和WT1-EWSR1拷贝）可能促成了DSRCT的疾病发病机制和/或演变。我们的研究表明，综合分子细胞遗传学方法鉴定出了EWSR1-WT1协同分子事件和预后遗传标记。因此，可以将FISH和M-CGH很好地应用于大量患者，以阐明DSRCT的基因组背景。
