Genetic heterogeneity and enrichment of variants in DNA-repair genes in ameloblastoma.

Document Type

Article

Publication Date

3-2023

Identifier

DOI: 10.1111/jop.13410

Abstract

OBJECTIVE: Ameloblastomas are a group of relatively common odontogenic tumors that frequently originate from the dental epithelium. These tumors are aggressive in nature and present as slow-growing painless cortical expansion of the jaw. Histologically, the follicular and plexiform subtypes constitute two-thirds of solid/multicystic ameloblastomas. The objective of this study was to understand the genetic architecture of follicular and plexiform ameloblastomas using deep whole-exome sequencing.

METHODS: Archived formalin-fixed paraffin-embedded tissue blocks of follicular (n = 4) and plexiform (n = 6) ameloblastomas were retrieved and genomic DNAs were isolated from the tumor tissue dissected from the formalin-fixed paraffin-embedded block. The exomes were enriched using the Integrated DNA Technologies Exome Research Panel (IDT, Coralville, IA) and paired-end sequencing was completed on an Illumina NovaSeq 6000 with an average output of 20 GB of data resulting in a mean coverage of 400×. Variant analysis was completed using custom-developed software: Rapid Understanding of Nucleotide variant Effect Software and variant integration and knowledge interpretation in genomes.

RESULTS: Our analyses focused on examining somatic variants (gnomAD minor allele frequency ≤1%) in genes found on an Food and Drug Administration -approved clinical cancer sequencing panel (FoundationOne®CDx). In follicular tumors, variants (>20% of the reads) were identified in BRAF, KMT2D, and ABL1 genes. In plexiform tumors, variants (>20% of the reads) were identified in ALK, BRAF, KRAS, KMT2D, SMO, KMT2A, and BRCA2 genes. Enrichment analysis showed a significant role of DNA repair genes in the development of these tumors.

CONCLUSION: The variants identified in follicular and plexiform ameloblastomas were enriched in DNA-repair genes. The observed genetic heterogeneity in these ameloblastomas may contribute to the aggressive nature and recurrence risk of these tumors.

Journal Title

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology

Volume

52

Issue

3

First Page

263

Last Page

270

MeSH Keywords

Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Genetic Heterogeneity; Odontogenic Tumors; Formaldehyde

Keywords

ameloblastoma; gene expression; tumors

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