Supplementary Material for: False-Negative Testing for <i>FIP1L1::</i><i>PDGFRA</i> by Fluorescence in situ Hybridization Is a Frequent Cause of Diagnostic Delay

The imatinib-sensitive fusion gene <i>FIP1L1::PDGFRA</i> is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of <i>PDGFRA</i>-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for <i>FIP1L1::PDGFRA</i>. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for <i>FIP1L1::PDGFRA</i>. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of <i>PDGFRA</i>-associated disease.

对伊马替尼敏感的FIP1L1::PDGFRA融合基因（FIP1L1::PDGFRA）是嗜酸性粒细胞髓系肿瘤患者中最常检出的分子异常。鉴于伊马替尼疗法问世前，血小板源性生长因子受体α（PDGFRA）相关髓系肿瘤的预后极差，快速识别该融合突变至关重要。本文报告1例因诊断延迟，最终因嗜酸性粒细胞性心内膜心肌纤维化接受心脏移植的患者。此次诊断延迟的部分原因，是针对FIP1L1::PDGFRA的荧光原位杂交（fluorescence in situ hybridization，FISH）检测结果呈假阴性。为进一步探究该问题，我们对确诊或疑似嗜酸性粒细胞髓系肿瘤的患者队列展开回顾分析，结果发现另有8例患者，其FIP1L1::PDGFRA逆转录聚合酶链反应（reverse-transcriptase polymerase chain reaction，RT-PCR）检测结果呈阳性，但FISH检测结果为阴性。更为关键的是，假阴性的FISH检测结果使患者接受伊马替尼治疗的中位时间延迟了257天。上述数据表明，对于临床特征提示PDGFRA相关疾病的患者，经验性伊马替尼治疗具有重要临床意义。

搜集汇总

背景与挑战

背景概述

该数据集是研究论文的补充材料，聚焦于FIP1L1::PDGFRA融合基因的假阴性荧光原位杂交测试问题，强调这常导致嗜酸性粒细胞性骨髓肿瘤患者的诊断延迟，并指出假阴性结果使伊马替尼治疗中位延迟257天，突显了临床及时干预的重要性。