Mouse anti-Human USP6 monoclonal antibody, clone 2G6

Background information. Cancer cells are characterized by their intrinsic ability to rapidly divide and migrate and to invade other tissues. How these processes are regulated at a molecular level is largely unknown. Results. Here, we identify the oncogenic TBC (Tre-2/Bub2/Cdc16) domain protein USP6 (also termed TRE17) as a regulator of both cell migration and division. We show that manipulating USP6 expression levels alters the ability of cells to migrate and to divide. Furthermore, we observe that cell proliferation and progression through cytokinesis depend on USP6 expression via a pathway that involves the small GTPase Arf6 and its GTPase-activating protein ACAP1. Conclusions. Our data suggest a model whereby the oncogenic potential of USP6 is linked to its ability to integrate cell migration and cytokinesis by regulating Arf6/ACAP1.

Patient: Female, 39-year-old Final Diagnosis: Atypical meningioma . meningioma . multiple meningioma Symptoms: Headache Medication: Clinical Procedure: Surgery and radiotherapy Specialty: Neurosurgery Objective: Unusual clinical course Background: The pathogenesis of sporadic multiple meningiomas in the patients without history of neurofibromatosis type II remains unclear. We report whole exome sequencing (WES) of 2 metachronous multiple meningiomas of the same patient. Case Report: A 39-year-old female had a 5-month history of headache and her magnetic resonance imaging (MRI) revealed a significantly enhanced intracranial space-occupying pathology with dura tail sign and skull invasion. She had no history of neurofibromatosis type II or other tumors. Tumor resection achieved Simpson grade I and the pathological studies revealed an atypical meningioma. After surgery, she accepted focal external-beam radiation therapy. One year later, MRI showed a significantly enhanced intracranial space-occupying pathology near the primary site of the previous tumor. She had only a mild headache. Simpson grade I resection of the tumor was achieved. The pathological diagnosis was still an atypical meningioma. WES on both tumors identified 220 common somatic gene mutations and 43 different somatic gene mutations. Three deleterious mutated genes including QRICH2, KIF2C, and MUC16 were identified only in the first tumor, and 9 deleterious mutated genes including FCGBP, RPS6KA5, GOLGA6L2, IGHV3-66, RPTN, AGRN, USP6, CLTCL1, and PABPC3 were identified only in the second tumor. As shown by the identical result of 3 prediction tools, RPS6KA5 and AGRN were most likely to be related to the progress of multiple atypical meningiomas. Conclusions: The metachronous meningiomas with same World Health Organization (WHO) grades in the same patient could have distinct genetic aberration patterns. The roles of RPS6KA5 and AGRN in the rapid progress of multiple atypical meningiomas need further studies.