Zou Ying S, Hoppman Nicole L, Singh Zeba N, Sawhney Sameer, Kotiah Sandy D, Baer Maria R
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Cancer Genet. 2017 Apr;212-213:38-44. doi: 10.1016/j.cancergen.2017.03.004. Epub 2017 Mar 27.
We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a 150 kb genomic region containing three genes, including NUMA1. Mate pair sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in protein homodimerization and heteroassociation) and tyrosine kinase domains of PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17) translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB fusion is the second instance of rearrangement of NUMA1, encoding an element of the mitotic apparatus, in human cancer.
我们报告了一名61岁患有嗜酸性粒细胞增多的骨髓增殖性肿瘤患者中存在NUMA1-PDGFRB融合基因，该患者对甲磺酸伊马替尼治疗有反应。通过中期染色体分析鉴定出涉及5q32和11q13.4带的t(5;11)染色体易位，并使用PDGFRB断裂分离探针组通过荧光原位杂交（FISH）证实了5q32上血小板衍生生长因子受体β（PDGFRB）基因的重排。对PDGFRB融合伴侣基因进行细菌人工染色体（BAC）FISH定位，将11q13.4处的断点缩小到一个包含三个基因（包括NUMA1）的150 kb基因组区域。配对测序分析证实了NUMA1-PDGFRB融合。该融合蛋白包括核有丝分裂装置蛋白1（NuMA1，参与蛋白质同型二聚化和异型缔合）的卷曲螺旋结构域和PDGFRB的酪氨酸激酶结构域。在伴有嗜酸性粒细胞增多的髓系和淋巴系肿瘤中已鉴定出涉及PDGFRB基因的多种重排，但核有丝分裂装置蛋白1（NUMA1）基因的重排此前仅在一例人类恶性肿瘤中报道过，即一名急性早幼粒细胞白血病患者因t(11;17)易位导致的NUMA1-RARA融合。NUMA1-PDGFRB融合是NUMA1重排的第二例，NUMA1编码有丝分裂装置的一个元件，见于人类癌症。
