Mutations of ARID1B, PIK3C2B, KMT2B, and FAT1 genes influence clinical outcome in newly diagnosed myeloma

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics Pub Date : 2024-11-01 DOI:10.1016/j.cancergen.2024.11.001

Marta Morawska, Michał Kiełbus, Magdalena Paziewska, Monika Szelest, Agnieszka Karczmarczyk, Joanna Zaleska, Paulina Własiuk, Krzysztof Giannopoulos, Norbert Grząśko

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引用次数: 0

Abstract

The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes. A total of 724 high-quality variants were validated. All patients harbored mutations associated with the RTK-RAS pathway, with over half having alterations in PI3 K, NOTCH, and WNT pathways. Several gene mutations were associated with specific clinical characteristics and prognostic indicators, revealing a complex interplay between genetic alterations and myeloma type, standard prognostic indicators, biochemical parameters, and renal function. Genetic alterations significantly influencing progression-free survival concerned PIK3C2B, ARID1B genes, and concomitant mutations in KMT2B, FAT1, and ARID1B. The findings underscore the potential of gene mutation-based prognostic tools in enhancing clinical decision-making and suggest that further exploration of identified genetic markers could pave the way for improved prognostic stratification and targeted therapeutic interventions in multiple myeloma.

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ARID1B、PIK3C2B、KMT2B和FAT1基因突变会影响新诊断骨髓瘤的临床结果。

该研究旨在阐明新诊断的多发性骨髓瘤患者的基因突变谱，以了解基因突变与临床预后的相关性。该研究共招募了20名患者，并使用TruSight Oncology 500 DNA试剂盒进行了基因突变分析。鉴定出的基因改变与临床病理特征和治疗效果相关。共验证了 724 个高质量变异。所有患者都存在与RTK-RAS通路相关的基因突变，超过一半的患者存在PI3 K、NOTCH和WNT通路的基因突变。一些基因突变与特定的临床特征和预后指标相关，揭示了基因改变与骨髓瘤类型、标准预后指标、生化指标和肾功能之间复杂的相互作用。对无进展生存期有重大影响的基因改变涉及PIK3C2B和ARID1B基因，以及KMT2B、FAT1和ARID1B的伴随突变。这些发现强调了基于基因突变的预后工具在加强临床决策方面的潜力，并表明进一步探索已确定的遗传标记物可为改善多发性骨髓瘤的预后分层和靶向治疗干预铺平道路。

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

Cancer Genetics ONCOLOGY-GENETICS & HEREDITY

CiteScore

3.20

自引率

5.30%

发文量

167

审稿时长

27 days

期刊介绍： The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor.