Carcinoma ex-pleomorphic adenoma derived from recurrent pleomorphic adenoma shows important difference by array CGH compared to recurrent pleomorphic adenoma without malignant transformation

Author(s)

Fernanda Viviane Mariano ^[1] ; Karina Giovanetti ^[2] ; Luis Fernando Vidal Saccomani ^[3] ; André Del Negro ^[4] ; Luiz Paulo Kowalski ^[5] ; Ana Cristina Victorino Krepischi ^[6] ; Albina Altemani ^[7]

Affiliation

^[1] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Patologia - Brasil

^[2] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Patologia - Brasil

^[3] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Patologia - Brasil

^[4] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Cirurgia de Cabeça e Pescoço - Brasil

^[5] AC Camargo Câncer Center. Departamento de Cirurgia de Cabeça e Pescoço - Brasil

^[6] Universidade de São Paulo. Instituto de Biociências. Departamento de Genética e Biologia Evolutiva - Brasil

^[7] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Patologia - Brasil

• Document type: Journal article
• Source: Brazilian Journal of Otorhinolaryngology; v. 82, n. 6, p. 687-694, 2016-12-00.

Abstract

Abstract Introduction: A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. Objective: We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. Methods: DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. Results: No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. Conclusion: The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation. (AU)

• FAPESP's process: 11/23204-5 - Genomic profile study of carcinoma ex-pleomorphic adenoma by array-comparative genomic hybridization
• Grantee: Albina Messias de Almeida Milani Altemani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/23366-5 - Genomic profile study of carcinoma ex-pleomorphic adenoma by array-comparative genomic hybridization
• Grantee: Fernanda Viviane Mariano Brum Corrêa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral