Molecular analysis to demonstrate that odontogenic keratocysts are neoplastic.
BACKGROUND
Odontogenic keratocysts (OKCs) are unique odontogenic lesions that have the potential to behave aggressively, that can recur, and that can be associated with the nevoid basal cell carcinoma syndrome. Whether they are developmental or neoplastic continues to be debated.


OBJECTIVE
To identify loss of heterozygosity of tumor suppressor genes in OKCs and to suggest a pathogenetic origin for these lesions.


METHODS
We examined 10 OKCs for loss of heterozygosity of tumor suppressor genes, using a microdissection and semiquantitative genotyping analysis. The genes analyzed included 10 common tumor suppressor genes, as well as the PTCH gene, which is mutated in nevoid basal cell carcinoma syndrome.


RESULTS
Loss of heterozygosity was seen in 7 of 10 cases, with a frequency between 11% and 80% of the genes studied. The genes that exhibited the most frequent allelic losses were p16, p53, PTCH, and MCC (75%, 66%, 60%, and 60%, respectively). Daughter cysts were associated with a higher frequency of allelic loss (P =.02), but epithelial budding was not.


CONCLUSIONS
Our study indicates that a significant number of OKCs show clonal loss of heterozygosity of common tumor suppressor genes. The finding of clonal deletion mutations of genomic DNA in these cysts supports the hypothesis that they are neoplastic rather than developmental in origin.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pa 15213, USA.
Narasimhan P
NP
Agaram
Bobby M
BM
Collins
Leon
L
Barnes
Deren
D
Lomago
Dalal
D
Aldeeb
Patricia
P
Swalsky
Sydney
S
Finkelstein
Jennifer L
JL
Hunt
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009807:Odontogenic Cysts / Q000235:genetics* / Q000473:pathology