Whole-exome sequencing of transforming oral lichen planus reveals mutations in DNA damage repair and apoptosis pathway genes.
Apoptosis
/ genetics
Carcinoma, Squamous Cell
/ diagnosis
DNA Damage
/ genetics
Head and Neck Neoplasms
/ complications
Humans
Lichen Planus
/ pathology
Lichen Planus, Oral
/ metabolism
Membrane Proteins
Mouth Neoplasms
/ pathology
Mutation
Nerve Tissue Proteins
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck
Exome Sequencing
cancer genetics
carcinogenesis
genomics
lichen planus
oral squamous cell carcinoma
Journal
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
ISSN: 1600-0714
Titre abrégé: J Oral Pathol Med
Pays: Denmark
ID NLM: 8911934
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
revised:
13
12
2021
received:
09
11
2021
accepted:
05
01
2022
pubmed:
12
2
2022
medline:
23
4
2022
entrez:
11
2
2022
Statut:
ppublish
Résumé
Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus-derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation. Using rigorous diagnostic criteria, we retrospectively identified patients with non-transforming oral lichen planus (i.e., known to be non-transforming with 5 years of clinical follow-up; n = 17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n = 9), or oral squamous cell carcinoma arising in lichen planus (n = 17). Gene mutational profiles derived from whole-exome sequencing on fixed mucosal specimens were compared among the groups. The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non-transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus-associated oral squamous cell carcinomas. These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus-related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non-transforming oral lichen planus.
Sections du résumé
BACKGROUND
BACKGROUND
Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus-derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation.
METHODS
METHODS
Using rigorous diagnostic criteria, we retrospectively identified patients with non-transforming oral lichen planus (i.e., known to be non-transforming with 5 years of clinical follow-up; n = 17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n = 9), or oral squamous cell carcinoma arising in lichen planus (n = 17). Gene mutational profiles derived from whole-exome sequencing on fixed mucosal specimens were compared among the groups.
RESULTS
RESULTS
The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non-transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus-associated oral squamous cell carcinomas.
CONCLUSIONS
CONCLUSIONS
These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus-related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non-transforming oral lichen planus.
Substances chimiques
Membrane Proteins
0
Nerve Tissue Proteins
0
TENM3 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
395-404Subventions
Organisme : British Association of Dermatologist's Geoffrey Dowling Fellowship
Organisme : Mayo Clinic Appignani Lichen Planus Benefactor Gift
Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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