Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis.
BACKGROUND
Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors.


METHODS
We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status. RT-qPCR was applied in four selected genes (B4GALT1, BAG1, PKD1L2, and PPP2R5A) covered by rare alterations, also including three MA and four normal oral tissues.


RESULTS
Fifty-seven CNAs and cnLOH were observed in the ameloblastomas and six CNAs in the AC. Seven of the CNAs were rare (six in UA and one in MA), four of them encompassing genes (gains of 7q11.21, 1q32.3, and 9p21.1 and loss of 16q23.2). We found positive correlation between rare CNA gene dosage and the expression of B4GALT1, BAG1, PKD1L2, and PPP2R5A. The AC and 1 UA were BRAF wild-type; however, this UA showed rare genomic alterations encompassing genes associated with RAF/MAPK activation.


CONCLUSIONS
Ameloblastomas show rare CNAs and cnLOH, presenting a specific genomic profile with no overlapping of the rare alterations among UA, MA, and AC. These genomic changes might play a role in tumor evolution and in BRAFV600E-negative tumors.
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil.
Marina Gonçalves
MG
Diniz
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil.
Alessandra Pires
AP
Duarte
International Center for Research - CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil.|Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia - UnB, Brasilia, DF, Brazil.
Rolando A
RA
Villacis
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil.
Bruna V A
BVA
Guimarães
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil.
Luiz Cláudio Pires
LCP
Duarte
Clinical Genetics Department and Institute of Regional Health, University of Southern Denmark, Odense, Denmark.|Urology Department, Faculty of Medicine, UNESP, Botucatu, SP, Brazil.
Sílvia R
SR
Rogatto
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais-UFMG, Belo Horizonte, MG, Brazil.
Ricardo Santiago
RS
Gomez
Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Geras-UFMG, Belo Horizonte, MG, Brazil.
Carolina Cavaliéri
CC
Gomes
D000293:Adolescent; D000328:Adult; D000564:Ameloblastoma / Q000235:genetics*; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D006801:Humans; D007573:Jaw Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
ameloblastic carcinoma; ameloblastoma; odontogenic tumor; whole-genome microarray