Genetic determinants of hearing loss associated with vestibular schwannomas

Konstantina M. Stankovic, MacIej M. Mrugala, Robert L. Martuza, Michael Silver, Rebecca Betensky, Joseph B. Nadol, Anat O. Stemmer-Rachamimov

Research output: Contribution to journalArticle

Abstract

HYPOTHESIS: The severity of hearing loss (HL) associated with vestibular schwannomas (VSs) is influenced by genes expressed by the VSs. BACKGROUND: Hearing loss is the most common presenting symptoms in patients with VSs, yet its pathophysiology remains elusive. Previous studies have suggested that VSs cause HL not only by inducing degeneration of the auditory nerve by compression but also by promoting degeneration of the inner ear. This study aimed to determine whether there is a molecular basis for differences in HL associated with VSs. METHODS: Surgical specimens of VSs were collected from 13 patients and were divided into a group associated with good (word recognition >70% and pure-tone average ≤30 dB) or poor hearing. Whole-genome expression profiling of VSs was performed with the Affymetrix GeneChip Human X3P Array. The expression of select genes was validated using real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Because of a small sample size, exact nonparametric tests were used to assess the association between good versus poor hearing and specific histological features of the tumors and patient demographics. RESULTS: Using gene set enrichment analysis, the chromosomal region 3q27 was found to be significantly different between the 2 groups of tumors. This region includes peroxisomal biogenesis factor 5-like gene, which was underexpressed in VSs with poor hearing. The expression of 3 other genes from different chromosomes was significantly different between the 2 groups: RAD54B, prostate-specific membrane antigen-like, and carcinoembryonic antigen. CONCLUSION: This study identified several molecular alterations in VSs stratified by hearing. These alterations may determine the severity of HL associated with VSs and may represent potential therapeutic targets to prevent or reduce HL in theses patients.

Original languageEnglish (US)
Pages (from-to)661-667
Number of pages7
JournalOtology and Neurotology
Volume30
Issue number5
DOIs
StatePublished - Aug 1 2009

Fingerprint

Acoustic Neuroma
Hearing Loss
Hearing
Genes
Cochlear Nerve
Carcinoembryonic Antigen
Inner Ear
Sample Size
Reverse Transcription
Neoplasms
Chromosomes
Immunohistochemistry
Demography
Genome
Gene Expression
Polymerase Chain Reaction

Keywords

  • Carcinoembryonic antigen
  • Hearing loss
  • Peroxisomal biogenesis factor 5-like
  • Platelet factor 4
  • Prostate-specific membrane antigen-like
  • RAD54B
  • Vestibular schwannoma

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Clinical Neurology
  • Sensory Systems

Cite this

Stankovic, K. M., Mrugala, M. M., Martuza, R. L., Silver, M., Betensky, R., Nadol, J. B., & Stemmer-Rachamimov, A. O. (2009). Genetic determinants of hearing loss associated with vestibular schwannomas. Otology and Neurotology, 30(5), 661-667. https://doi.org/10.1097/MAO.0b013e3181a66ece

Genetic determinants of hearing loss associated with vestibular schwannomas. / Stankovic, Konstantina M.; Mrugala, MacIej M.; Martuza, Robert L.; Silver, Michael; Betensky, Rebecca; Nadol, Joseph B.; Stemmer-Rachamimov, Anat O.

In: Otology and Neurotology, Vol. 30, No. 5, 01.08.2009, p. 661-667.

Research output: Contribution to journalArticle

Stankovic, KM, Mrugala, MM, Martuza, RL, Silver, M, Betensky, R, Nadol, JB & Stemmer-Rachamimov, AO 2009, 'Genetic determinants of hearing loss associated with vestibular schwannomas', Otology and Neurotology, vol. 30, no. 5, pp. 661-667. https://doi.org/10.1097/MAO.0b013e3181a66ece
Stankovic, Konstantina M. ; Mrugala, MacIej M. ; Martuza, Robert L. ; Silver, Michael ; Betensky, Rebecca ; Nadol, Joseph B. ; Stemmer-Rachamimov, Anat O. / Genetic determinants of hearing loss associated with vestibular schwannomas. In: Otology and Neurotology. 2009 ; Vol. 30, No. 5. pp. 661-667.
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