Faculty Opinions recommendation of Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system.

Author(s):  
Martine Roussel
2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Daniella Bello-Germino ◽  
Rasmey Chhin ◽  
Thu Tran ◽  
Tetyana L. Vasylyeva

Hypomelanosis of Ito is a neurocutaneous disorder characterized by skin manifestations in a characteristic pattern associated with musculoskeletal and central nervous system symptoms. Our patient was diagnosed with Wilms’ tumor stage I at age two and was also found to have distinct streaked areas of skin hyper- and hypopigmentation suggestive of Hypomelanosis of Ito. We believe that our patient’s clinical diagnoses of Hypomelanosis of Ito and Wilms’ tumor are interlinked. The connecting factor is yet to be identified. Our patient does not have a deletion of 11p13 associated with a defect in WT1, the Wilms’ tumor suppressor gene. As such, it is quite possible that what made her more susceptible to the development of Wilms’ tumor was her Hypomelanosis of Ito, which is implicated in a number of other organ dysfunctions.


2015 ◽  
Vol 68 ◽  
pp. 272-283 ◽  
Author(s):  
Matthew T. Simpson ◽  
Ishwariya Venkatesh ◽  
Ben L. Callif ◽  
Laura K. Thiel ◽  
Denise M. Coley ◽  
...  

Neurosurgery ◽  
2013 ◽  
Vol 72 (6) ◽  
pp. 930-935 ◽  
Author(s):  
Sven Gläsker ◽  
Marie T. Krüger ◽  
Jan-Helge Klingler ◽  
Marcin Wlodarski ◽  
Julia Klompen ◽  
...  

Abstract BACKGROUND: Neurogenic polyglobulia occurs with central nervous system hemangioblastomas. Among the suggested mechanisms are extramedullary hematopoiesis in the tumor tissue and germline mutations of the von Hippel-Lindau (VHL) tumor suppressor gene. OBJECTIVE: To determine the frequency and driving mechanisms of polyglobulia in central nervous system hemangioblastomas. METHODS: We performed a retrospective analysis of pre- and postoperative (at 3 and 12 months) hemoglobin levels in a consecutive series of patients with hemangioblastomas operated on in our institution from 1996 to 2009. We performed molecular genetic analyses for mutations of the VHL tumor suppressor gene. RESULTS: Preoperative hemoglobin levels were available from 164 patients. The average hemoglobin level (15.2 g/dL in males and 13.1 g/dL in females) was within normal range according to our standards. Of 22 patients with increased preoperative hemoglobin levels (>17 g/dL in males and >15 g/dL in females), 8 presented with pathological hemoglobin (>18.5 g/dL in males and >16.5 g/dL in females) according to World Health Organization criteria. Surgical removal of the hemangioblastoma resulted in a permanent cure of polyglobulia in all patients. Six of the 8 patients with pathological hemoglobin elevation carried a germline mutation of the VHL tumor suppressor gene. CONCLUSION: Neurogenic polyglobulia occurs in a subset of patients with hemangioblastomas. This phenomenon is mostly observed in VHL mutation carriers, but also occurs in patients with sporadic hemangioblastomas. Removal of the tumor results in the permanent cure of polyglobulia. Our observations suggest that polyglobulia is an effect by the tumor itself, either due to paraneoplasia or extramedullary hematopoiesis.


2015 ◽  
Vol 112 (37) ◽  
pp. E5169-E5178 ◽  
Author(s):  
Ieva Gailite ◽  
Birgit L. Aerne ◽  
Nicolas Tapon

The Hippo (Hpo) pathway is a highly conserved tumor suppressor network that restricts developmental tissue growth and regulates stem cell proliferation and differentiation. At the heart of the Hpo pathway is the progrowth transcriptional coactivator Yorkie [Yki–Yes-activated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) in mammals]. Yki activity is restricted through phosphorylation by the Hpo/Warts core kinase cascade, but increasing evidence indicates that core kinase-independent modes of regulation also play an important role. Here, we examine Yki regulation in the Drosophila larval central nervous system and uncover a Hpo/Warts-independent function for the tumor suppressor kinase liver kinase B1 (LKB1) and its downstream effector, the energy sensor AMP-activated protein kinase (AMPK), in repressing Yki activity in the central brain/ventral nerve cord. Although the Hpo/Warts core cascade restrains Yki in the optic lobe, it is dispensable for Yki target gene repression in the late larval central brain/ventral nerve cord. Thus, we demonstrate a dramatically different wiring of Hpo signaling in neighboring cell populations of distinct developmental origins in the central nervous system.


2014 ◽  
Vol 35 (10) ◽  
pp. 2164-2174 ◽  
Author(s):  
Tsung-Han Hsieh ◽  
Chen-Li Chien ◽  
Yu-Hsiu Lee ◽  
Chen-I Lin ◽  
Jui-Yu Hsieh ◽  
...  

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