染色体碎裂（cth）是基因组不稳定性的一种形式，导致一次性灾难性事件中大规模从头结构性染色体重排。它可以导致促进癌症的改变，例如肿瘤抑制基因序列的丢失、致癌融合的形成和致癌基因的扩增。我们调查了儿童 T 细胞急性淋巴细胞白血病 (T-ALL) 患者的 cth 遗传背景和临床意义。为此，我们使用高密度微阵列对 173 名新诊断 T-ALL 儿童的全基因组拷贝数变化进行了分析。在 10 个 T-ALL 样本 (5.78%) 中鉴定出 Cth。其中 6 例中，cth 发生于奈梅亨断裂综合征 (n = 5) 或 Li-Fraumeni 综合征 (n = 1) 的体质背景。 Cth 产生改变，包括 CDKN2A/B (n = 4) 和 EZH2 (n = 4) 的删除、CDK6 (n = 2) 的扩增以及 NUP214::ABL1 和 TFG::GPR128 融合。 Cth 阳性白血病表现出肿瘤抑制基因 RB1 (n = 3)、TP53 (n = 1) 和 MED12 (n = 2) 的缺失。 Cth 阳性 T-ALL 患者的 5 年总生存 (OS) 概率较低 [0.56 vs. 0.81；风险比 (HR) = 4.14 (1.42-12.02) p = 0.017] 5 年无事件生存率也是如此 [0.45 vs. 0.74； HR = 3.91（1.52-10.08）； p = 0.012]。染色体碎裂是儿科 T-ALL 中罕见的基因组现象，但与癌症诱发综合征显着相关，并可能与较差的预后相关。© 2024。作者。

Chromothripsis (cth) is a form of genomic instability leading to massive de novo structural chromosome rearrangements in a one-time catastrophic event. It can cause cancer-promoting alterations, such as loss of sequences for tumor-suppressor genes, formation of oncogenic fusions, and oncogene amplifications. We investigated the genetic background and clinical significance of cth in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. For this purpose, whole-genome copy number alterations were analyzed in 173 children with newly diagnosed T-ALL using high-density microarrays. Cth was identified in 10 T-ALL samples (5.78%). In six of them, cth occurred in a constitutional background of Nijmegen breakage syndrome (n = 5) or Li-Fraumeni syndrome (n = 1). Cth generated alterations, including deletions of CDKN2A/B (n = 4) and EZH2 (n = 4), amplifications of CDK6 (n = 2), and NUP214::ABL1 and TFG::GPR128 fusions. Cth-positive leukemias exhibited deletions involving the tumor-suppressor genes RB1 (n = 3), TP53 (n = 1) and MED12 (n = 2). Cth-positive T-ALL patients had a lower probability of 5-year overall survival (OS) [0.56 vs. 0.81; hazard ratio (HR) = 4.14 (1.42-12.02) p = 0.017] as did 5-year event-free survival [0.45 vs. 0.74; HR = 3.91 (1.52-10.08); p = 0.012]. Chromothripsis is an infrequent genomic phenomenon in pediatric T-ALL but is significantly associated with cancer-predisposing syndromes and may associate with inferior prognosis.© 2024. The Author(s).