Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor
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...
Saved in:
Published in | Human cell : official journal of Human Cell Research Society Vol. 37; no. 5; pp. 1602 - 1609 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Singapore
Springer Nature Singapore
01.09.2024
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Report-3 ObjectType-Case Study-4 |
ISSN: | 1749-0774 0914-7470 1749-0774 |
DOI: | 10.1007/s13577-024-01106-6 |