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Click here to search FindAPhD.com for PhD studentship opportunities(MBRC) Identification of common genetic modifiers of risk of vestibular schwannoma (acoustic neuroma)
Prof G Evans, Dr M Smith
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Vestibular schwannomas arise from the 8th cranial nerve and are normally isolated tumours that occur in older adults. Bilateral vestibular schwannomas are a hallmark of neurofibromatosis type 2 (NF2) disease. Vestibular schwannomas carry a lifetime risk of balance problems and profound to complete hearing loss, requiring treatment by hearing aids or rehabilitation with auditory brainstem/cochlear implants1. Surgery is used to remove vestibular schwannomas where possible, and radiation is used for sporadic vestibular schwannomas when they have surgical morbiditiesor with patient choice; however, the outcome of radiation therapy is worse for individuals with NF2-associated vestibular schwannomas than for those with a sporadic tumour. Vestibular schwannomas have a low rate of association with predisposing mutations2, but those occurring in within the context of NF2 disease tend to occur earlier in life. In addition, our recent studies have identified new areas of clinical phenotypic overlap between NF2 disease and LZTR1-associated schwannomatosis3,4, indicating that LZTR1 mutations can cause unilateral vestibular schwannoma. Vestibular schwannomas have traditionally been included in the exclusion criteria for diagnosis of schwannomatosis. These studies highlight the importance of genetic diagnosis, which in some cases can be the only way to distinguish between sporadic vestibular schwannoma, mosaic NF2 and LZTR1-associated schwannomatosis, and indicate the usefulness of stratifying risk for age at onset.
Our current study will determine genetic modifiers for risk of earlier age at onset of VS and identify novel mechanisms of schwannoma initiation. This will aid clinical management of affected individuals with a particular genetic variant or a particular set of risk variants and may identify members of the general population at high risk of VS that warrants MRI screening.
Our current study will determine genetic modifiers for risk of earlier age at onset of VS and identify novel mechanisms of schwannoma initiation. This will aid clinical management of affected individuals with a particular genetic variant or a particular set of risk variants and may identify members of the general population at high risk of VS that warrants MRI screening.
Funding Notes
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Applicants must be from the UK/EU and funding covers fees/stipend for three years commencing September 2018. Applicants may contact the Primary Supervisor directly with any questions. Online applications must be submitted, select 'Manchester BRC' as the programme - for more information on how to apply please visit https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mbrc-studentships/
Applicants must be from the UK/EU and funding covers fees/stipend for three years commencing September 2018. Applicants may contact the Primary Supervisor directly with any questions. Online applications must be submitted, select 'Manchester BRC' as the programme - for more information on how to apply please visit https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mbrc-studentships/
References
1. Evans DG, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol. Jan 2005;26(1):93-97
2. Pathmanaban ON, Sadler KV, Kamaly-Asl ID, King AT, Rutherford SA, Hammerbeck-Ward C, McCabe MG, Kilday JP, Beetz C, Poplawski NK, Evans DG, Smith MJ. Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in Children and Young Adults. JAMA Neurol. 2017;74(9):1123-1129.
3. Smith MJ, Isidor B, Beetz C, Williams SG, Bhaskar SS, Richer W, O'Sullivan J, Anderson B, Daly SB, Urquhart JE, Fryer A, Rustad CF, Mills SJ, Samii A, du Plessis D, Halliday D, Barbarot S, Bourdeaut F, Newman WG, Evans DG. Mutations in LZTR1 add to the complex heterogeneity of schwannomatosis. Neurology. Jan 13 2015;84(2):141-147.
4. Smith MJ, Bowers NL, Bulman M, Gokhale C, Wallace AJ, King AT, Lloyd SK, Rutherford SA, Hammerbeck-Ward CL, Freeman SR, Evans DG. Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis. Neurology. 2017;88:87-92.
2. Pathmanaban ON, Sadler KV, Kamaly-Asl ID, King AT, Rutherford SA, Hammerbeck-Ward C, McCabe MG, Kilday JP, Beetz C, Poplawski NK, Evans DG, Smith MJ. Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in Children and Young Adults. JAMA Neurol. 2017;74(9):1123-1129.
3. Smith MJ, Isidor B, Beetz C, Williams SG, Bhaskar SS, Richer W, O'Sullivan J, Anderson B, Daly SB, Urquhart JE, Fryer A, Rustad CF, Mills SJ, Samii A, du Plessis D, Halliday D, Barbarot S, Bourdeaut F, Newman WG, Evans DG. Mutations in LZTR1 add to the complex heterogeneity of schwannomatosis. Neurology. Jan 13 2015;84(2):141-147.
4. Smith MJ, Bowers NL, Bulman M, Gokhale C, Wallace AJ, King AT, Lloyd SK, Rutherford SA, Hammerbeck-Ward CL, Freeman SR, Evans DG. Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis. Neurology. 2017;88:87-92.
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