Premium
Rare copy number alterations and copy‐neutral loss of heterozygosity revealed in ameloblastomas by high‐density whole‐genome microarray analysis
Author(s) -
Diniz Marina Gonçalves,
Duarte Alessandra Pires,
Villacis Rolando A.,
Guimarães Bruna V. A.,
Duarte Luiz Cláudio Pires,
Rogatto Sílvia R.,
Gomez Ricardo Santiago,
Gomes Carolina Cavaliéri
Publication year - 2017
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12505
Subject(s) - loss of heterozygosity , ameloblastoma , copy number variation , comparative genomic hybridization , biology , gene dosage , cancer research , microarray , pathology , gene , microbiology and biotechnology , genetics , medicine , genome , gene expression , allele , maxilla , anatomy
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. Conclusion 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.