Ramos-Campoy Silvia, Puiggros Anna, Kamaso Joanna, Beà Sílvia, Bougeon Sandrine, Larráyoz María José, Costa Dolors, Parker Helen, Rigolin Gian Matteo, Blanco María Laura, Collado Rosa, Ancín Idoya, Salgado Rocío, Moro-García Marco A, Baumann Tycho, Gimeno Eva, Moreno Carol, Salido Marta, Calvo Xavier, Calasanz María José, Cuneo Antonio, Nguyen-Khac Florence, Oscier David, Haferlach Claudia, Strefford Jonathan C, Schoumans Jacqueline, Espinet Blanca
Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain.
Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
Cancers (Basel). 2022 Jul 29;14(15):3715. doi: 10.3390/cancers14153715.
Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic microarrays were compared and the prognostic value of cth was analyzed. Cth was distributed throughout the genome, with chromosomes 3, 6 and 13 being those most frequently affected. OGM detected 88.1% of the previously known copy number alterations and several additional cth-related rearrangements (median: 9, range: 3-26). Two patterns were identified: one with rearrangements clustered in the region with cth (3/9) and the other involving both chromothriptic and non-chromothriptic chromosomes (6/9). Cases with cth showed a shorter time to first treatment (TTFT) than non-cth patients (median TTFT: 2 m vs. 15 m; = 0.013). However, when stratifying patients based on status, cth did not affect TTFT. Only maintained its significance in the multivariate analysis for TTFT, including cth and genome complexity defined by genomic microarrays (HR: 1.60; = 0.029). Our findings suggest that abnormalities, rather than cth itself, underlie the poor prognosis observed in this subset.
染色体碎裂（cth）与慢性淋巴细胞白血病（CLL）患者的不良结局和不良预后因素相关。尽管与高基因组不稳定性相关，但先前的研究尚未评估cth在基因组复杂性背景下的作用。在此，我们分析了33例患有cth的CLL患者队列，并将其与129例具有复杂核型的非cth病例队列进行比较。对9例cth病例使用光学基因组图谱（OGM）进行分析。比较基因组微阵列检测到的模式，并分析cth的预后价值。Cth分布于整个基因组，3号、6号和13号染色体是最常受影响的染色体。OGM检测到88.1%的先前已知拷贝数改变以及一些额外的与cth相关的重排（中位数：9，范围：3 - 26）。识别出两种模式：一种是重排在cth区域聚集（3/9），另一种涉及染色体碎裂和非染色体碎裂的染色体（6/9）。患有cth的病例首次治疗时间（TTFT）比非cth患者短（中位TTFT：2个月对15个月；P = 0.013）。然而，根据状态对患者进行分层时，cth不影响TTFT。只有在TTFT的多变量分析中保持其显著性，包括cth和由基因组微阵列定义的基因组复杂性（HR：1.60；P = 0.029）。我们的研究结果表明，异常，而非cth本身，是该亚组中观察到的不良预后的基础。
