Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma. Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient. This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient’s bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma. These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.

中文翻译：

---

卵巢无性细胞瘤先发的侵袭性系统性肥大细胞增多症

侵袭性系统性肥大细胞增多症（ASM）是一种罕见的恶性疾病，其特征是肥大细胞在各个器官中堆积紊乱。我们在这里描述了一位既往有卵巢无性细胞瘤病史的女性 ASM 患者。进行分子细胞基因组分析以阐明该患者的 ASM 和无性细胞瘤之间的病因学联系。该患者患有卵巢无性细胞瘤，通过化疗和手术切除进行治疗。随后两年完全缓解后，她出现了 ASM 症状。在她的骨髓中检测到 KIT 基因体细胞 D816A 突变，这有助于诊断 ASM。出乎意料的是，在先前的卵巢无性细胞瘤样本中也检测到了这种 KIT D816A 变异。全外显子组测序使我们能够鉴定出骨髓中 TP53 基因的体细胞无义突变，但无性细胞瘤中却没有。患者骨髓的微阵列分析显示 TP53 基因座出现拷贝数中性杂合性缺失，提示 TP53 基因存在纯合无义突变。此外，在无性细胞瘤中也检测到TP53位点杂合性缺失。这些结果表明，在该病例中引起 ASM 的肥大细胞要么起源于先前的卵巢无性细胞瘤，作为残留肿瘤细胞的克隆进化，获得了 TP53 突变，要么两个肿瘤都是由携带 TP53 突变的共同癌症干细胞发展而来。套件 D816A 变体。