Comprehensive Study of Chromosomal Copy Number Variations and Genomic Variations Predicting Overall Survival in Myelodysplastic Syndromes.

IF 2.5 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2024-01-01 Epub Date: 2024-03-05 DOI:10.1159/000536446

Nehakumari Maurya, Chandrakala Shanmukhaiah, Somprakash Dhangar, Manisha Madkaikar, Babu Rao Vundinti

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引用次数: 0

Abstract

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia. The disease progression is majorly affected by genetic defects. However, about 40-50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence, there remains a room to advance the biological understanding and find molecular prognostic markers for cytogenetically normal MDS.

Methods: We performed a high-resolution CGH + SNP array along with next-generation sequencing (NGS) of 77 primary diagnosed MDS patients, and also they were clinically followed up.

Results: Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity, i.e., MDS-biTP53, as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI: 0.37-21) when analyzed by Kaplan-Meier survival analysis.

Conclusion: CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients, respectively, with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact.

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预测骨髓增生异常综合征总生存率的染色体 CNV 和基因组变异综合研究

简介骨髓增生异常综合征（MDS）是一种异质性疾病，以全血细胞减少、骨髓发育不良为特征，并有发展为急性髓性白血病（AML）的倾向。疾病的发展主要受遗传缺陷的影响。然而，约 40%-50% 的 MDS 患者核型正常，但病情发展各不相同。因此，对于细胞遗传学正常（CN）的 MDS，我们仍需加深生物学理解并寻找分子预后标志物：我们对 77 例初诊 MDS 患者进行了高分辨率 CGH + SNP 阵列和 NGS 分析，并对他们进行了临床随访：结果：我们的研究在 49% 的 MDS 患者中发现了 82 个具有临床意义的基因组病变（丢失/增殖）。CGH + SNP 阵列将正常核型的比例降低了 30%。SNP 阵列结合 NGS 证实了 TP53 基因（2/6）的双偶功能缺失，这是一种临床相关的生物标志物，也是基于基因的 MDS 新实体，即 2022 年世界卫生组织新分类中的 MDS-biTP53。基因组 2p22.3 区域病变频繁，通过卡普兰-梅耶尔生存分析，其危险比（2.7，95% CI 0.37 - 21）也更高：CGH+SNP阵列分别改变了18%和13%患者的细胞遗传学和IPSS-R风险分组，改善了预后预测。这项研究强调了 MDS 的细胞遗传异质性，并指出 2 号染色体异常可能对诊断和预后产生影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.