TY - JOUR
T1 - Genome sequencing reveals molecular subgroups in oral epithelial dysplasia
AU - Márquez, Agustín
AU - Mujica, Isidora
AU - Jordan, Natalia
AU - Baez, Pablo
AU - Tarquinio, Sandra
AU - Santos, Jean Nunes Dos
AU - Adorno-Farias, Daniela
AU - Martínez, Benjamín
AU - Morales-Pison, Sebastián
AU - Fernandez-Ramires, Ricardo
N1 - © 2023, Brazilian Oral Research. All Rights Reserved.
PY - 2023
Y1 - 2023
N2 - This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: “HGD-like cluster” with 4HGD and 2LGD and “LGD-like cluster” with 4 LGD. MLL4 pathogenic variants were exclusively in the “LGD-like cluster”. TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.
AB - This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: “HGD-like cluster” with 4HGD and 2LGD and “LGD-like cluster” with 4 LGD. MLL4 pathogenic variants were exclusively in the “LGD-like cluster”. TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.
KW - Carcinoma in Situ
KW - High-Throughput Nucleotide Sequencing
KW - Molecular Sequence Annotation
KW - Mouth Neoplasms
KW - Mutation
KW - Precancerous Conditions
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85163922783&origin=resultslist&sort=plf-f&src=s&sid=e1c7e067c1aab3974779edf6c11dfd49&sot=b&sdt=b&s=TITLE-ABS-KEY%28Genome+sequencing+reveals+molecular+subgroups+in+oral+epithelial+dysplasia%29&sl=89&sessionSearchId=e1c7e067c1aab3974779edf6c11dfd49&relpos=0
U2 - 10.1590/1807-3107BOR-2023.VOL37.0063
DO - 10.1590/1807-3107BOR-2023.VOL37.0063
M3 - Article
SN - 1806-8324
VL - 37
SP - 1
EP - 15
JO - Brazilian Oral Research
JF - Brazilian Oral Research
M1 - e063
ER -