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

Marina Gonçalves Diniz, Alessandra Pires Duarte, Rolando A Villacis, Bruna V A Guimarães, Luiz Cláudio Pires Duarte, Sílvia R Rogatto, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of Oral Pathology & Medicine
Vol/bind46
Sider (fra-til)371-376
ISSN0904-2512
DOI
StatusUdgivet - 2017

Fingeraftryk

Ameloblastoma
Neoplasms
Mutation

Citer dette

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. / Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis. I: Journal of Oral Pathology & Medicine. 2017 ; Bind 46. s. 371-376.
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title = "Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis",
abstract = "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.",
author = "Diniz, {Marina Gon{\cc}alves} and Duarte, {Alessandra Pires} and Villacis, {Rolando A} and Guimar{\~a}es, {Bruna V A} and Duarte, {Luiz Cl{\'a}udio Pires} and Rogatto, {S{\'i}lvia R} and Gomez, {Ricardo Santiago} and Gomes, {Carolina Cavali{\'e}ri}",
note = "{\circledC} 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2017",
doi = "10.1111/jop.12505",
language = "English",
volume = "46",
pages = "371--376",
journal = "Journal of Oral Pathology & Medicine",
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Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis. / 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.

I: Journal of Oral Pathology & Medicine, Bind 46, 2017, s. 371-376.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis

AU - Diniz, Marina Gonçalves

AU - Duarte, Alessandra Pires

AU - Villacis, Rolando A

AU - Guimarães, Bruna V A

AU - Duarte, Luiz Cláudio Pires

AU - Rogatto, Sílvia R

AU - Gomez, Ricardo Santiago

AU - Gomes, Carolina Cavaliéri

N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1111/jop.12505

DO - 10.1111/jop.12505

M3 - Journal article

VL - 46

SP - 371

EP - 376

JO - Journal of Oral Pathology & Medicine

JF - Journal of Oral Pathology & Medicine

SN - 0904-2512

ER -