Clonality and heterogeneity of pulmonary blastoma from the viewpoint of genetic alterations: A case report

SummaryBiphasic pulmonary blastoma is a rare lung tumor with epithelial and mesenchymal components. Genetic alterations in this tumor are largely unknown, except for the presence of β-catenin and p53 mutations and the absence of KRAS mutation. To understand the molecular process of histogenesis of this tumor, a whole genome allelic imbalance (AI) scanning using a high-resolution single nucleotide polymorphism array as well as mutational analysis of the p53, EGFR, KRAS and β-catenin genes were performed against the epithelial and mesenchymal components in the primary tumor and a metastatic tumor in a case of pulmonary blastoma. AI at chromosome regions 14q24-q32 and 17p11-p13 and β-catenin mutation were commonly detected in all tumors. On the other hand, AI at chromosome regions 3p11-p14 and 9p21-p24 and p53 mutation were detected only in the mesenchymal component in the primary tumor but not in the epithelial component in the primary tumor and the brain metastasis. Likewise, AI at chromosome regions 6p24-p25 and 6q14-q27 was detected in the epithelial component in the primary tumor and the brain metastasis but not in the mesenchymal component in the primary tumor. Furthermore, the genetic alterations detected in the metastatic tumor were completely the same as those in the epithelial component in the primary tumor, indicating that a tumor cell(s) in the epithelial component in the primary tumor selectively metastasized to the brain. These results indicate that this biphasic tumor is of monoclonal origin and the phenotypic heterogeneity of the tumor is due to the differences in the accumulated genetic alterations in each component of the tumor.