Genetic determinants of hearing loss associated with vestibular schwannomas.
OBJECTIVE
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 < or =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.


CONCLUSIONS
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.
Stankovic
Konstantina M
KM
Department of Otolaryngology and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. konstantina_stankovic@meei.harvard.org
Mrugala
Maciej M
MM
Martuza
Robert L
RL
Silver
Michael
M
Betensky
Rebecca A
RA
Nadol
Joseph B
JB
Stemmer-Rachamimov
Anat O
AO
D000293:Adolescent; D000328:Adult; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006309:Hearing / Q000235:genetics; D034381:Hearing Loss / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000150:complications* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA; D004247:DNA