Rare copy number alterations and copy‐neutral loss of heterozygosity revealed in ameloblastomas by high‐density whole‐genome microarray analysis

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Ameloblastomas are benign aggressive epithelial odontogenic tumors and can infiltrate normal adjacent bone, leading to bone destruction and facial deformities. Ameloblastomas occur mainly in the posterior mandible and present two main variants: unicystic ameloblastoma (UA), which is encapsulated, and the infiltrative form, the multicystic ameloblastoma (MA). Ameloblastic carcinomas (AC) are the malignant counterpart of ameloblastomas, either resulting from the malignant transformation of ameloblastomas or arising de novo. In a similar manner to ameloblastomas, AC generally occurs at the posterior mandible 1. Recently, the oncogenic BRAFV600E mutation was described to be recurrent in MA 2 and UA 3, as well as in AC 3.
Somatic copy number alterations (CNAs), which result from deletions, insertions or duplications, and copy‐neutral loss of heterozygosity (cnLOH), are common genomic changes in cancer 6. cnLOH arises by uniparental disomy (UPD) or deletion of one copy and compensatory duplication of the other allele 7. Over the past years, germ line copy number variations (CNVs) and cnLOH have been associated with risk and pathogenesis of several complex diseases and cancer types, including breast and colorectal cancer 7.
To our knowledge, chromosomal alterations in ameloblastomas were reported in two studies that used comparative genomic hybridization (CGH). Jääskeläinen et al. 10 showed alterations in two of 17 ameloblastomas, while Toida et al. 11 detected alterations in one of nine ameloblastomas evaluated. In addition, loss of chromosome 22 was detected by fluorescent in situ hybridization (FISH) in eight of the nine ameloblastomas 11. Furthermore, a low frequency of chromosomal aberrations was reported in AC (approximately one in nine cases), including gain of 5q 12 and chromosome 7 trisomy found in one patient with peripheral ameloblastoma 13.
In this study, we report the genomic profiling of benign and malignant odontogenic neoplasms (UA, MA, and AC) using high‐density whole‐genome microarray and evaluated the results according to the BRAFV600E mutation status. Our aim is to better understand the biology of these tumors and to identify potential molecular markers underlying behavioral differences.
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