Effects of temozolomide on tumor mutation burden and microsatellite instability in melanoma cells.
exome sequencing
immune checkpoint inhibitors
melanoma
microsatellite instability
temozolomide
Journal
The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545
Informations de publication
Date de publication:
02 Sep 2023
02 Sep 2023
Historique:
revised:
28
07
2023
received:
23
06
2023
accepted:
01
08
2023
medline:
2
9
2023
pubmed:
2
9
2023
entrez:
2
9
2023
Statut:
aheadofprint
Résumé
The efficacy of combination therapy with an immune checkpoint inhibitor (ICI) and cytotoxic chemotherapeutic agents has been investigated in cancer, including melanoma. Before ICIs were introduced, dacarbazine or temozolomide (TMZ) were used to treat melanoma. Several studies using glioma or colorectal cancer cells showed that TMZ can increase the tumor mutation burden (TMB) and induce mismatch repair (MMR) deficiency associated with microsatellite instability (MSI). These could increase immunoreactivity to an ICI, but this has not been evaluated in melanoma cells. We investigated the effects of TMZ on MSI status and TMB in melanoma cells. To evaluate the TMB, we performed whole-exome sequencing using genomic DNA from the human melanoma cell lines Mel18, A375, WM266-4, G361, and TXM18 before and after TMZ treatment. Polymerase chain reaction amplification of five mononucleotide repeat markers, BAT25, BAT26, NR21, NR24, and MONO27, was performed, and we analyzed changes in the MSI status. In all cell lines, the TMB was increased after TMZ treatment (the change amount of TMB with ≤ 5% variant allele frequency [VAF] was 18.0-38.3 mutations per megabase) even in the condition without obvious cytological damage. MSI after TMZ treatment was not observed in any cells. TMZ increased TMB but did not change MSI status in melanoma cells.
Identifiants
pubmed: 37658676
doi: 10.1111/1346-8138.16925
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Japanese Dermatological Association.
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