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Case Reports
. 2024 Oct;63(10):e23276.
doi: 10.1002/gcc.23276.

Establishment and Characterization of a Novel Pleuropulmonary Blastoma Cell Line

Keisuke Kato  1   2   3 , Hiroaki Goto  4   5 , Mio Tanaka  1   5 , Tetsuomi Suzuki  4 , Yasunori Toyoda  4 , Masato Shinkai  5   6 , Norihiko Kitagawa  5   6 , Toshiji Nishi  6 , Hisato Kigasawa  4 , Kenji Kurosawa  7 , Noriko Aida  8 , Ai Yoshimi  2   3 , Asami Noda  3 , Yumi Ito  9 , Masafumi Seki  10 , Junko Takita  11 , Noriyuki Nagahara  12 , Masahiro Tsuchida  2   3 , Yukichi Tanaka  1
Affiliations
Case Reports

Establishment and Characterization of a Novel Pleuropulmonary Blastoma Cell Line

Keisuke Kato et al. Genes Chromosomes Cancer. 2024 Oct.

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.

Keywords: DICER1; bortezomib; pleuropulmonary blastoma.

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References

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