Proto-oncogene mutations in middle ear cholesteatoma contribute to its pathogenesis.
Cholesteatoma
Exome analysis
Gene mutation
Notch 1
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
15 11 2023
15 11 2023
Historique:
received:
20
03
2023
accepted:
22
08
2023
medline:
17
11
2023
pubmed:
16
11
2023
entrez:
16
11
2023
Statut:
epublish
Résumé
Chronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations. DNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399). This is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.
Sections du résumé
BACKGROUND
Chronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations.
RESULTS
DNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399).
CONCLUSIONS
This is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.
Identifiants
pubmed: 37968650
doi: 10.1186/s12920-023-01640-6
pii: 10.1186/s12920-023-01640-6
pmc: PMC10647096
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
288Informations de copyright
© 2023. The Author(s).
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