Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
Genes Chromosomes Cancer. 2024 Jul;63(7):e23260. doi: 10.1002/gcc.23260.
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.
神经母细胞瘤（NB）是一种具有异质性的儿童癌症，男孩的发病率略高于女孩，其性别差异的原因尚不清楚。鉴于越来越多的证据表明 Y 染色体丢失（LoY）参与包括癌症在内的男性疾病，我们研究了 NB 中的 Y 染色体状态。使用 Cytoscan HD SNP 微阵列分析了来自瑞典队列的男性 NB 肿瘤样本。分析了 70 个 NB 肿瘤的 Y 染色体非整倍体，这些数据与其他遗传、生物学和临床参数相关。在 21%的男性 NB 肿瘤中发现了 LoY，并且几乎仅在具有高危基因组谱的肿瘤中发现。此外，LoY 与诊断时年龄的增加有关，并且在具有 11q 缺失和激活端粒维持机制的肿瘤中富集。相比之下，具有 MYCN 扩增基因组谱的肿瘤保留了它们的 Y 染色体。对癌症中 LoY 的理解有限，使得难以得出结论 LoY 是 NB 的驱动事件还是增加基因组不稳定性的功能。对男性 NB 肿瘤中 Y 染色体基因的基因表达分析显示，某些与总生存率较差相关的基因表达较低。编码组蛋白去甲基酶的 KDM5D 是进一步研究的一个有趣候选基因。已经表明 LoY 会影响非生殖组织中常染色体基因座的表观基因组层，并且已经报道 KDM5D 在不同的恶性肿瘤中下调和/或与不良预后相关。需要进一步研究来探索 LoY 在 NB 中的机制和功能后果。
