Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance
(2024) In Genes Chromosomes and Cancer 63(7). p.1-10- Abstract
Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased... (More)
Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an MYCN-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. KDM5D, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and KDM5D has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.
(Less)
- author
- publishing date
- 2024-07
- type
- Contribution to journal
- publication status
- published
- keywords
- 11q-deletion, chromosome Y, LoY, neuroblastoma, telomere maintenance, TERT
- in
- Genes Chromosomes and Cancer
- volume
- 63
- issue
- 7
- article number
- e23260
- pages
- 1 - 10
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:39031441
- scopus:85199017948
- ISSN
- 1045-2257
- DOI
- 10.1002/gcc.23260
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.
- id
- 31d6d7b6-a5ad-4641-84ca-e84aae93db4e
- date added to LUP
- 2024-08-30 05:45:47
- date last changed
- 2024-08-31 03:00:20
@article{31d6d7b6-a5ad-4641-84ca-e84aae93db4e,
abstract = {{<p>Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an MYCN-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. KDM5D, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and KDM5D has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.</p>}},
author = {{Djos, Anna and Svensson, Johanna and Gaarder, Jennie and Umapathy, Ganesh and Nilsson, Staffan and Ek, Torben and Vogt, Hartmut and Georgantzi, Kleopatra and Öra, Ingrid and Träger, Catarina and Kogner, Per and Martinsson, Tommy and Fransson, Susanne}},
issn = {{1045-2257}},
keywords = {{11q-deletion; chromosome Y; LoY; neuroblastoma; telomere maintenance; TERT}},
language = {{eng}},
number = {{7}},
pages = {{1--10}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Genes Chromosomes and Cancer}},
title = {{Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance}},
url = {{http://dx.doi.org/10.1002/gcc.23260}},
doi = {{10.1002/gcc.23260}},
volume = {{63}},
year = {{2024}},
}