Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome

• Published in: Genes chromosomes & cancer Vol. 51; no. 9; pp. 890 - 897
• Main Authors: Li, Feng, Zhai, Yong-Ping, Tang, Yu-Mei, Wang, Li-Ping, Wan, Pin-Jun
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2012
• Subjects: Adult; Amino Acid Sequence; Base Sequence; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 8 - genetics; Humans; In Situ Hybridization, Fluorescence; Male; Molecular Sequence Data; Myeloproliferative Disorders - genetics; Nuclear Pore Complex Proteins - genetics; Oncogene Proteins, Fusion - genetics; Prognosis; Proto-Oncogene Proteins - genetics; Real-Time Polymerase Chain Reaction; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Translocation, Genetic - genetics
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.21973

The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm caused by the fusion of various partner genes to fibroblast growth factor receptor 1 (FGFR1). Various FGFR1 fusions are associated with subtly distinct disease phenotypes. Here, we report a new translocation at the FGFR1 locus in a patient who carried t(1;8)(q25;p11.2) and presented with myeloproliferative neoplasm‐like symptoms. The patient was characterized by myeloid hyperplasia of bone marrow, markedly elevated numbers of monocytes, and normal to mildly elevated eosinophils. Initial fluorescent in situ hybridization analysis confirmed that FGFR1 in this patient was disrupted. Subsequent analysis led to the identification of a novel translocation, in which exon 23 of the translocated promoter region (TPR) gene at chromosome band 1q25 was fused to exon 13 of FGFR1 (RefSeq NM_0231102.2). The TPR portion of the fusion protein contains putative functional motifs including an N‐terminal TprMet domain, nuclear pore complexes associating domain, and multiple coiled‐coil domains. It is likely that one or more of the motifs from TPR contribute to dimerization, resulting in constitutive activation of the FGFR1 kinase domain. Our results further support a critical role of FGFR1 in the pathogenesis of EMS and may lead to more accurate diagnosis and potential targeted therapy. © 2012 Wiley Periodicals, Inc.