背景：人们早已认识到癌症发病率、结果和治疗反应方面的性别差异。通过分析两性之间大规模癌症样本的体细胞突变谱，揭示了一些具有性别差异的癌症潜在驱动因素。然而，仍然需要深入研究基因组不稳定性的性别偏见特征，以将个体癌症类型的临床差异联系起来。方法：在这里，我们利用了一个已发布的框架，该框架旨在专门比较两组之间的拷贝数概况，以确定癌症基因组图谱计划数据库中 16 种癌症类型中性别偏见的拷贝数改变 (CNA)，并剖析了那些CNA。结果：总共在 16 种癌症类型中发现了 81 个男性偏向的 CNA 区域和 23 个女性偏向的 CNA 区域。功能注释分析表明，与性别偏向 CNA 相关的几个关键生物学功能在多种癌症类型中是共有的，包括免疫相关途径和细胞信号传导的调节。大多数性别偏向的 CNA 对转录结果有重大影响，平均超过 68% 的基因与跨癌症类型的 CNA 具有线性关系，其中 14% 的基因受到性别和拷贝数组合的影响。此外，29 个性别偏向的 CNA 区域显示出潜在的作为性别特异性预后生物标志物的能力，例如 11q13.4 上的头颈癌和肺癌的 CNA。结论：该分析通过详细描述不同癌症基因组不稳定性中的性别差异，为性别在癌症病因和预后中的作用提供了新的见解。版权所有 © 2024 Chenhao Zhang 等人。

Background: Sex difference has long been recognized at cancer incidence, outcomes, and responses to therapy. Analyzing the somatic mutation profiles of large-scale cancer samples between the sexes have revealed several potential drivers of cancer with sex difference. However, it is still a demand for in-depth scrutinizing the sex-biased characteristics of genome instability to link the clinical differences for individual cancer type. Methods: Here, we utilized a published framework devised to specifically compare the copy number profiles between 2 groups to identify the sex-biased copy number alterations (CNAs) across 16 cancer types from the The Cancer Genome Atlas Program database, and dissected the impact of those CNAs. Results: Totally, 81 male-biased CNA regions and 23 female-biased CNA regions in 16 cancer types were found. Functional annotation analysis showed that several critical biological functions associated with sex-biased CNAs are shared in multiple cancer types, including immune-related pathways and regulation of cellular signaling. Most sex-biased CNAs have a substantial effect on transcriptional consequence, where the average of over 68% of genes have a linear relationship with CNAs across cancer types, and 14% of those genes are affected by the combination of the sex and copy number. Furthermore, 29 sex-biased CNA regions show latent capacity to be sex-specific prognostic biomarker such as CNA on 11q13.4 for head and neck cancer and lung cancer. Conclusions: This analysis offers new insights into the role of sex in cancer etiology and prognosis through a detailed characterization of sex differences in genome instability of diverse cancers.Copyright © 2024 Chenhao Zhang et al.