Beyond myeloid neoplasms germline guidelines: Validation of the thresholds criteria in the search of germline predisposition variants

EJHaem Pub Date : 2024-10-02 DOI:10.1002/jha2.1012

Julia Mestre, Lorea Chaparro, Ana Manzanares, Blanca Xicoy, Lurdes Zamora, Francesc Sole, Oriol Calvete

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Abstract

Introduction

Germline predisposition to myeloid neoplasms can be suspected in patients younger than 50 years or when harboring mutations with a variant allele frequency (VAF) higher than 30% for point mutations in specific genes. To investigate the VAF thresholds’ accuracy we have explored the prevalence of germline variants below the 30% VAF threshold.

Methods

A total of 40 variants with VAF lower than 30% in bone marrow samples of myeloid neoplasm patients were selected and studied in CD3⁺ cells.

Results

All the selected variants were not found in CD3⁺ cells except one variant in the SF3B1 gene. However, the whole series was found somatic. Selected variants were also evaluated with our previously studied series of 52 variants with VAF higher than 30%.

Conclusion

Our study suggests that variants with VAF below 30% are strong somatic candidates but the variants with VAF higher than 30% cannot be considered of germline origin.

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髓系肿瘤种系外指南：种系易感性变异搜索中阈值标准的验证

导言：如果患者年龄小于 50 岁，或者特定基因点突变的变异等位基因频率（VAF）高于 30%，则可怀疑其具有髓系肿瘤的种系易感性。为了研究 VAF 临界值的准确性，我们探讨了低于 30% VAF 临界值的种系变异的发生率。方法在髓系肿瘤患者的骨髓样本中选择了 40 个 VAF 低于 30% 的变异，并在 CD3+ 细胞中进行了研究。结果除了 SF3B1 基因中的一个变异外，所有被选中的变异都没有在 CD3+ 细胞中发现。然而，整个系列的变异均为体细胞变异。所选变异还与我们之前研究的 VAF 高于 30% 的 52 个变异系列进行了评估。结论我们的研究表明，VAF 低于 30% 的变异是强有力的体细胞候选变异，但 VAF 高于 30% 的变异不能被认为是种系起源变异。

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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EJHaem

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