Research Program: The candidate hopes to eventually improve the diagnosis and treatment of vestibular schwannomas. He hypothesizes that the specific mutations in the NF2 tumor suppressor gene account for the clinical findings in these patients. The goals are to define: 1) the specific mutations present in the NF2 tumor suppressor gene, 2) the relation of specific mutations to clinical manifestations, and 3) the relation of specific mutations to cellular proliferation fractions. Studies will be carried out in 150 archived schwannomas from his collaborator groups. Clinical data will be obtained from chart reviews and x-ray studies.
In Specific Aim 1, heteroduplex analysis, single- strand conformation polymorphism (SSCP) and mRNA mutation analyses will be performed to determine types of mutations present. Flow cytometry and immunohistochemical analysis techniques will be used for measuring direct indicators of cellular proliferation in the tumor tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DC000114-02
Application #
2377554
Study Section
Communication Disorders Review Committee (CDRC)
Project Start
1996-03-01
Project End
2001-02-28
Budget Start
1997-03-01
Budget End
1998-02-28
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Ohio State University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Lasak, John M; Welling, D Bradley; Akhmametyeva, Elena M et al. (2002) Retinoblastoma-cyclin-dependent kinase pathway deregulation in vestibular schwannomas. Laryngoscope 112:1555-61
Chang, Long-Sheng; Akhmametyeva, Elena M; Wu, Yong et al. (2002) Multiple transcription initiation sites, alternative splicing, and differential polyadenylation contribute to the complexity of human neurofibromatosis 2 transcripts. Genomics 79:63-76
Welling, D Bradley; Lasak, John M; Akhmametyeva, Elena et al. (2002) cDNA microarray analysis of vestibular schwannomas. Otol Neurotol 23:736-48
Welling, D B; Nagaraja, H N (2000) Endolymphatic mastoid shunt: a reevaluation of efficacy. Otolaryngol Head Neck Surg 122:340-5
Massick, D D; Welling, D B; Dodson, E E et al. (2000) Tumor growth and audiometric change in vestibular schwannomas managed conservatively. Laryngoscope 110:1843-9
Welling, D B; Akhmametyeva, E M; Daniels, R L et al. (2000) Analysis of the human neurofibromatosis type 2 gene promoter and its expression. Otolaryngol Head Neck Surg 123:413-8
Welling, D B (1998) Clinical manifestations of mutations in the neurofibromatosis type 2 gene in vestibular schwannomas (acoustic neuromas). Laryngoscope 108:178-89