Mariano Fernanda Viviane, Gondak Rogério de Oliveira, Martins Antonio Santos, Coletta Ricardo Della, Paes de Almeida Oslei, Kowalski Luiz Paulo, Krepischi Ana Cristina Victorino, Altemani Albina
Pathology Department, Faculty of Medicine, State University of Campinas (UNICAMP), Campinas, Brazil.
Pathology Department, Faculty of Santa Catarina (UFSC), Florianópolis, Brazil.
Histopathology. 2015 Sep;67(3):410-5. doi: 10.1111/his.12655. Epub 2015 Mar 12.
Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes.
Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among others. The secondary MPA showed a genomic profile similar to that of the primary MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain).
Our findings indicated a clonal origin of the secondary MPA, as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome.
转移性多形性腺瘤（MPA）是一种罕见肿瘤，其转移机制尚不清楚。迄今为止，尚无关于MPA基因组学的研究。我们采用阵列比较基因组杂交技术分析原发性和继发性MPA，以确定体细胞拷贝数改变及受影响的基因。
对原发性（腮腺唾液腺）和继发性（头皮皮肤）MPA的肿瘤DNA样本进行阵列比较基因组杂交研究，并使用NEXUS COPY NUMBER DISCOVERY软件分析数据。原发性MPA显示拷贝数缺失影响3p22.2p14.3和19p13.3p123，以及6号染色体上四种不同缺失的复杂模式。3p缺失包含多个基因，包括CTNNB1、SETD2、BAP1和PBRM1等。继发性MPA显示出与原发性MPA相似的基因组图谱，伴有额外的拷贝数变化，影响9p24.3p13.1（缺失）、19q11q13.43（增益）和22q11.1q13.33（增益）。
我们的研究结果表明继发性MPA具有克隆起源，因为两种肿瘤共享常见的基因组拷贝数改变图谱。此外，我们能够在原发性肿瘤中检测到一种特定的拷贝数改变模式，该模式可以解释其转移特征，而继发性MPA显示出更不平衡的基因组。
