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Role of DFNA5 in hearing loss and cancer - a comment on Rakusic et al.

Croes L, Op de Beeck K, Van Camp G - Onco Targets Ther (2015)

View Article: PubMed Central - PubMed

Affiliation: Center of Medical Genetics (CMG), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium ; Center for Oncological Research (CORE), Department of Medicine, University of Antwerp, Antwerp, Belgium.

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We would like to comment on the paper published by Rakusic et al about sudden bilateral hearing loss in gastric cancer as the only symptom of disease... The authors state that “Inactivated DFNA5, otherwise described in hereditary bilateral deafness, perhaps favors the development of deafness in patients with gastric cancer”... We believe this conclusion is erroneous... The DFNA5 mutation leading to hearing loss is thought to be an activating, gain of function mutation... As the DFNA5 protein has an apoptosis inducing capacity, the effect is expected to be an increase in apoptosis, possibly leading to hearing loss by apoptosis of cells crucial for hearing, such as cochlear hair cells (Figure 1)... Therefore, in our opinion, the observed sudden bilateral deafness in the 60-year-old woman is not caused by inactivation of DFNA5... Akino et al showed that DFNA5 is methylated in 52% of primary gastric cancers and was correlated with positivity for Epstein–Barr virus and the absence of metastasis... In patients with metastasized gastric cancer the incidence of DFNA5 methylation was 16.7% (2/12)... The observation that DFNA5 is inactivated in this woman is thus not exceptional and in agreement with the literature.

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Possible mechanism of DFNA5 in hearing loss and cancer.
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Mentions: We would like to comment on the paper published by Rakusic et al about sudden bilateral hearing loss in gastric cancer as the only symptom of disease.1 The authors state that “Inactivated DFNA5, otherwise described in hereditary bilateral deafness, perhaps favors the development of deafness in patients with gastric cancer”.1 We believe this conclusion is erroneous. Although DFNA5 has been implicated in both hearing loss and cancer, the underlying molecular mechanisms are different and completely opposite (Figure 1).


Role of DFNA5 in hearing loss and cancer - a comment on Rakusic et al.

Croes L, Op de Beeck K, Van Camp G - Onco Targets Ther (2015)

Possible mechanism of DFNA5 in hearing loss and cancer.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592022&req=5

f1-ott-8-2613: Possible mechanism of DFNA5 in hearing loss and cancer.
Mentions: We would like to comment on the paper published by Rakusic et al about sudden bilateral hearing loss in gastric cancer as the only symptom of disease.1 The authors state that “Inactivated DFNA5, otherwise described in hereditary bilateral deafness, perhaps favors the development of deafness in patients with gastric cancer”.1 We believe this conclusion is erroneous. Although DFNA5 has been implicated in both hearing loss and cancer, the underlying molecular mechanisms are different and completely opposite (Figure 1).

View Article: PubMed Central - PubMed

Affiliation: Center of Medical Genetics (CMG), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium ; Center for Oncological Research (CORE), Department of Medicine, University of Antwerp, Antwerp, Belgium.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

We would like to comment on the paper published by Rakusic et al about sudden bilateral hearing loss in gastric cancer as the only symptom of disease... The authors state that “Inactivated DFNA5, otherwise described in hereditary bilateral deafness, perhaps favors the development of deafness in patients with gastric cancer”... We believe this conclusion is erroneous... The DFNA5 mutation leading to hearing loss is thought to be an activating, gain of function mutation... As the DFNA5 protein has an apoptosis inducing capacity, the effect is expected to be an increase in apoptosis, possibly leading to hearing loss by apoptosis of cells crucial for hearing, such as cochlear hair cells (Figure 1)... Therefore, in our opinion, the observed sudden bilateral deafness in the 60-year-old woman is not caused by inactivation of DFNA5... Akino et al showed that DFNA5 is methylated in 52% of primary gastric cancers and was correlated with positivity for Epstein–Barr virus and the absence of metastasis... In patients with metastasized gastric cancer the incidence of DFNA5 methylation was 16.7% (2/12)... The observation that DFNA5 is inactivated in this woman is thus not exceptional and in agreement with the literature.

No MeSH data available.


Related in: MedlinePlus