Ambele, Melvin AnyasiRobinson, LiamVan Heerden, M.B. (Marlene)Pepper, Michael SeanVan Heerden, Willem Francois Petrus2023-10-202023-01Ambele, M.A., Robinson, L., Van Heerden, M.B. et al. 2023, 'Comparative molecular genetics of odontogenic keratocysts in sporadic and syndromic patients', Modern Pathology, vol. 36, no. 1, art. 100002, doi : 10.1016/j.modpat.2022.100002.0893-3952 (print)1530-0285 (online)10.1016/j.modpat.2022.100002http://hdl.handle.net/2263/93011DATA AVAILABILITY STATEMENT : All data generated or analyzed during this study are included in this published article.Odontogenic keratocysts (OKCs) are common cysts of odontogenic origin that usually occur as a single nonsyndromic cyst in isolation (sporadic) or as syndromic multiple cysts as a manifestation of naevoid basal cell carcinoma syndrome. Alterations involving the PTCH gene are the most commonly identified factor associated with up to 85% and 84% of naevoid basal cell carcinoma syndrome and sporadic cases, respectively. Other Hedgehog pathway and non-Hedgehog pathway-associated genes have been implicated in the pathogenesis of OKCs. This pilot study used the Affymetrix OncoScan molecular assay to perform a comparative genomic analysis between 4 sporadic and 3 syndromic cases of OKC to identify molecular drivers that may be common and/or distinct in these 2 groups. The majority of alterations detected in both groups were copy number neutral loss of heterozygosity. Despite distinct molecular signatures observed in both groups, copy number neutral loss of heterozygosity alterations involving chromosome 9q affecting not only PTCH but also the NOTCH1 gene were detected in all syndromic and 3 sporadic cases. Loss of heterozygosity alterations involving 16p11.2 affecting genes not previously described in OKCs were also detected in all syndromic and 3 sporadic cases. Furthermore, alterations on 22q11.23 and 10q22.1 were also detected in both groups. Of note, alterations on 1p13.3, 2q22.1, and 6p21.33 detected in sporadic cases were absent in all syndromic cases. This study demonstrates that a more common group of genes may be affected in both groups of OKCs, whereas other alterations may be useful in distinguishing sporadic from syndromic cysts. These findings should be validated in larger OKC cohorts to improve molecular diagnosis and subsequent patient management.en© 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.. Notice : this is the author’s version of a work that was accepted for publication in Modern Pathology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Modern Pathology, vol. 36, no. 1, art. 100002, doi : 10.1016/j.modpat.2022.100002.Odontogenic keratocyst (OKC)Oral cancerNaevoid basal cell carcinoma syndrome (NBCCS)Gorlin–Goltz syndromeAffymetrix OncoScan molecular assayOdontogenic keratocystsMolecular geneticsSDG-03: Good health and well-beingPostprint Article