Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor.

Autor: Kato K; Divisions of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan. kkatoibaraki@gmail.com.; Division of Pediatric Hematology and Oncology, Institute of Pediatric Medicine and Cancer Research, Ibaraki Children's Hospital, Futaba-dai 3-3-1, Mito, Ibaraki, Japan. kkatoibaraki@gmail.com., Nagai JI; Divisions of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.; Clinical Laboratory, Kanagawa Children's Medical Center, Yokohama, Japan., Goto H; Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan., Shinkai M; Pediatric Surgery, Kanagawa Children's Medical Center, Yokohama, Japan., Kitagawa N; Pediatric Surgery, Kanagawa Children's Medical Center, Yokohama, Japan., Toyoda Y; Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan., Nishi T; Pediatric Surgery, Kanagawa Children's Medical Center, Yokohama, Japan., Kigasawa H; Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan., Tanaka M; Divisions of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan., Kurosawa K; Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan., Ito Y; Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Japan., Haruta M; Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan., Kamijo T; Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan., Yoshimi A; Division of Pediatric Hematology and Oncology, Institute of Pediatric Medicine and Cancer Research, Ibaraki Children's Hospital, Futaba-dai 3-3-1, Mito, Ibaraki, Japan., Tsuchida M; Division of Pediatric Hematology and Oncology, Institute of Pediatric Medicine and Cancer Research, Ibaraki Children's Hospital, Futaba-dai 3-3-1, Mito, Ibaraki, Japan., Nagahara N; Isotope Research Center, Nippon Medical School, Tokyo, Japan., Tanaka Y; Divisions of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
Jazyk: angličtina
Zdroj: Human cell [Hum Cell] 2024 Sep; Vol. 37 (5), pp. 1602-1609. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1007/s13577-024-01106-6
Abstrakt: The biological heterogeneity of neuroblastoma underscores the need for an in vitro model of each molecularly defined subgroup to investigate tumorigenesis and develop targeted therapies. We have established a permanently growing cell line from a 12-year-old girl who developed a late recurrent stage MS, MDM2-amplified neuroblastoma arising in the liver and performed histological, molecular, cytogenetic, exome, and telomere analyses of the recurrent tumor and the cell line. On histology, the recurrent tumor was immunoreactive for TP53, CDKN1A, and MDM2. A molecular cytogenetic study of the recurrent tumor revealed the amplification of MDM2 but no amplification of MYCN. The established cell line, NBM-SHIM, showed amplification of both MDM2 and MYCN on double-minute chromosomes. A copy number evaluation based on exome data confirmed the finding for MYCN and MDM2 and further identified high ploidy on CDK4 and GLI2 loci in the recurrent tumor and the cell line. The telomere maintenance mechanism on the cell line is unusual in terms of the low expression of TERT despite MYCN amplification and alternative lengthening of telomeres suggested by positive value for C-circle assay and telomere contents quantitative assay. The cell line is unique because it was established from a MYCN-nonamplified, MDM2-amplified, late-relapsed stage MS neuroblastoma, and MYCN amplification was acquired during cell culture. Therefore, the cell line is a valuable tool for investigating neuroblastoma tumorigenesis and new molecular targeted therapies for disrupted ARF-TP53-MDM2 pathway and amplification of MDM2 and CDK4.
(© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)
Databáze: MEDLINE
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