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58种肿瘤类型中59251例易位的染色体参与的独特特征。一种新视角。

Distinct Signatures of Chromosomal Involvement in 59 251 Translocations Across 58 Tumor Types. A Novel Perspective.

作者信息

Mitelman Felix, Mandahl Nils

机构信息

Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.

出版信息

Genes Chromosomes Cancer. 2025 May;64(5):e70053. doi: 10.1002/gcc.70053.

DOI:10.1002/gcc.70053
PMID:40346909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12065015/
Abstract

Chromosomal translocations are key events in cancer, driving oncogenesis by disrupting and deregulating critical genes. While specific tumor-associated translocations are well studied, the frequencies and distributions of most remain unknown. Additionally, the role of chromosomal reshuffling in translocations has received little attention. This study presents data on the chromosomal involvement in 59 251 translocations reported in 58 tumor entities, including both benign and malignant tumors. Unlike studies focusing on tumor-specific abnormalities identified at the chromosome band level, this study examines translocations at the chromosomal level, offering a novel perspective on their distribution. This broader approach aims to uncover patterns that do not emerge or are disregarded in studies limited to tumor-specific aberrations. The resulting dataset provides a novel resource for deepening our understanding of the chromosomal origins of translocations in neoplasia. Comparisons of translocation frequency distributions among tumor types, when excluding the characteristic tumor-associated translocations, revealed that the patterns of chromosomal involvement in translocations are largely unique to each tumor entity. Statistical analyses of 241 pairwise comparisons of translocation spectra within hematologic disorders, solid tumors, and between groups of hematologic malignancies and both benign and malignant solid tumors showed insignificant/very weak associations (R ≤ 0.3) in 98% of the comparisons. The findings hence demonstrate that different tumor types are characterized by distinct chromosomal translocation signatures, strongly suggesting that most translocations encountered in tumor cells are not merely random events. Consequently, our study highlights the potential of rare translocations to serve as indicators of disease-specific processes.

摘要

染色体易位是癌症中的关键事件,通过破坏和失调关键基因来驱动肿瘤发生。虽然特定的肿瘤相关易位已得到充分研究,但大多数易位的频率和分布仍不清楚。此外,染色体重排在易位中的作用很少受到关注。本研究提供了关于58种肿瘤实体(包括良性和恶性肿瘤)中报告的59251例易位的染色体参与情况的数据。与专注于在染色体带水平上鉴定的肿瘤特异性异常的研究不同,本研究在染色体水平上检查易位,为其分布提供了新的视角。这种更广泛的方法旨在揭示在仅限于肿瘤特异性畸变的研究中未出现或被忽视的模式。所得数据集为深化我们对肿瘤形成中易位的染色体起源的理解提供了新资源。在排除特征性肿瘤相关易位后,对肿瘤类型之间易位频率分布的比较表明,易位中染色体参与的模式在很大程度上因每个肿瘤实体而异。对血液系统疾病、实体瘤以及血液系统恶性肿瘤组与良性和恶性实体瘤组之间的易位谱进行的241对比较的统计分析显示,在98%的比较中,关联不显著/非常弱(R≤0.3)。因此,这些发现表明不同的肿瘤类型具有独特的染色体易位特征,强烈表明在肿瘤细胞中遇到的大多数易位不仅仅是随机事件。因此,我们的研究强调了罕见易位作为疾病特异性过程指标的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/c69abd4c5308/GCC-64-e70053-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/c2fce54e3d55/GCC-64-e70053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/0105360a378e/GCC-64-e70053-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/c69abd4c5308/GCC-64-e70053-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/c2fce54e3d55/GCC-64-e70053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/0105360a378e/GCC-64-e70053-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/12065015/c69abd4c5308/GCC-64-e70053-g003.jpg

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