Establishment and Characterization of a Novel Pleuropulmonary Blastoma Cell Line

• Published in: Genes chromosomes & cancer Vol. 63; no. 10; pp. e23276 - n/a
• Main Authors: Kato, Keisuke, Goto, Hiroaki, Tanaka, Mio, Suzuki, Tetsuomi, Toyoda, Yasunori, Shinkai, Masato, Kitagawa, Norihiko, Nishi, Toshiji, Kigasawa, Hisato, Kurosawa, Kenji, Aida, Noriko, Yoshimi, Ai, Noda, Asami, Ito, Yumi, Seki, Masafumi, Takita, Junko, Nagahara, Noriyuki, Tsuchida, Masahiro, Tanaka, Yukichi
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.10.2024; Wiley Subscription Services, Inc
• Subjects: Amino acid substitution; Animals; Bortezomib; Cell Line, Tumor; Chemotherapy; Child, Preschool; Children; Chromosome aberrations; Colorimetry; Cytogenetics; Cytotoxicity; DEAD-box RNA Helicases - genetics; DICER1; Drug development; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mice; Mice, Nude; Mutation; pleuropulmonary blastoma; Pulmonary Blastoma - genetics; Pulmonary Blastoma - pathology; Ribonuclease III - genetics; Thorax; Tumor Suppressor Protein p53 - genetics; Tumors; bortezomib; pleuropulmonary blastoma; DICER1
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.23276

ABSTRACT Purpose Pleuropulmonary blastoma (PPB) is an infrequently encountered childhood malignant intrathoracic neoplasm associated with unfavorable clinical behavior. Since a well‐characterized preclinical model is essential for developing competent agents for PPB, we aim to establish and characterize the world's first cell line of PPB, and attempt to perform the cytotoxicity assay on the PPB cell line. Experimental Design The index case is a 2‐year‐old female who developed a right thoracic tumor that was surgically removed and treated with multi‐agent chemotherapy. The patient is free from recurrence, although it was 9 years after the diagnosis when she developed a thyroid tumor. We performed in vitro cultivation of the isolated neoplastic cells from the tumor, cytogenetic findings and molecular analysis, and tetrazolium colorimetric assay. Result The histology was consistent with PPB. Serial passage of cultivation produced a continuously growing cell line, KCMC‐PPB‐1. Conventional cytogenetic analysis of the established cell line revealed complex numerical and structural chromosomal abnormalities, including add(17)(p11). Mutation analysis on the cultured cells revealed amino‐acid substitution mutation on exon 4 of TP53 (NM_001276760.3:c.212_213delTG; NP_001263689.1:p.Leu72ArgfsTer37) and compound heterozygous mutations of DICER1 (NM_177438.3:c. 4910C>A; NP_803187.1:Ser1637* and NM_177438.3:c. 5114A>T; NP_803187.1:Glu1705Val). The cultivated cells demonstrated vulnerability to bortezomib on cytotoxicity assay. Conclusion Our KCMC‐PPB‐1 is the first genuine, molecularly characterized PPB cell line. The cell line is transplantable to nu/nu mice; therefore, it is suitable for a preclinical model for new drug development. The cytotoxicity assay demonstrated that bortezomib is active in the current PPB model.