Systemic mastocytosis (SM) is a myeloproliferative neoplasm displaying abnormal mast cell proliferation. It is subdivided into different forms, including aggressive systemic mastocytosis (ASM) and systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Oncogenic genetic alterations include point mutations, mainly the D816V, conferring poor prognosis and therapy resistance, and fusion genes, with those involving / as the most recurrent events. We here describe an ASM case negative to the D816V and V617F alterations but showing a frameshift heterozygous mutation and the co-occurrence of three fusion transcripts. The first one, was generated by a balanced t(4;5)(q24;q32) translocation as the sole abnormality. Other two novel chimeras, and originated from cryptic intra-chromosomal abnormalities. The patient rapidly evolved towards SM-AHN, characterized by the persistence of the chimera, due to the presence of an extra copy of the der(5)t(4;5)(q24;q34) chromosome and an increase in the mutation allelic frequency.

中文翻译：

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侵袭性系统性肥大细胞增多症，同时存在 PRKG2::PDGFRB、KAT6A::NCOA2 和 RXRA::NOTCH1 融合转录本以及杂合 RUNX1 移码突变

系统性肥大细胞增多症（SM）是一种骨髓增生性肿瘤，表现为肥大细胞增殖异常。它分为不同的形式，包括侵袭性系统性肥大细胞增多症（ASM）和伴有相关血液肿瘤的系统性肥大细胞增多症（SM-AHN）。致癌基因改变包括点突变，主要是D816V，导致不良预后和治疗抵抗，以及融合基因，其中涉及/是最经常发生的事件。我们在这里描述了一个 D816V 和 V617F 改变阴性的 ASM 病例，但显示移码杂合突变和三个融合转录本的共现。第一个是由作为唯一异常的平衡 t(4;5)(q24;q32) 易位产生的。另外两种新颖的嵌合体，起源于神秘的染色体内异常。由于 der(5)t(4;5)(q24;q34) 染色体的额外拷贝的存在以及突变等位基因的增加，患者迅速向 SM-AHN 进化，其特征是嵌合体的持续存在频率。