Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors
Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors
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DOI：
10.1002/gcc.22803
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发表时间：
2019-08-31
影响因子：
3.7
通讯作者：
Antonescu, Cristina R.
中科院分区：
文献类型：
--
作者：
Dickson, Brendan C.;Chung, Catherine T-S;Antonescu, Cristina R.
肺泡软部肉瘤是一种罕见的恶性肿瘤，自其最初的描述以来，仍然是一种组织发生不确定的肿瘤。表征ASPS诊断的疾病定义分子事件是ASPSCR1-TFE3融合基因。在确定了一例具有新型TFE3融合伴侣的ASPS索引病例后，我们进行了回顾性审查，以确定这是否代表一个孤立事件。我们确定了另外两个病例，总共有三个病例缺乏ASPSCR1伴侣。患者平均年龄为46岁（17-65岁）；两名患者为女性。发病部位包括横结肠、足部和硬脑膜。每个病例都表现出典型的ASPS组织形态，所有病例的免疫组织化学均为TFE3阳性。指标患者的常规分子检测显示HNRNPH3-TFE3基因融合；其余病例发现有DVL2-TFE3或prc - tfe3融合产物。后两种融合先前已在肾细胞癌中发现；据我们所知，这是首次报道HNRNPH3-TFE3基因融合。这些发现突出了迄今为止未被充分认识的ASPS遗传多样性，其似乎与易位相关的肾细胞癌和PEComa的分子重叠更广泛。这些结果对ASPS的诊断具有直接意义，因为依赖于ASPSCR1的检测可能产生假阴性结果。虽然这些发现进一步了解了ASPS的分子发病机制，但与这种罕见肿瘤的组织发生有关的问题仍未解决。
Alveolar soft part sarcoma (ASPS) is a rare malignancy that, since its initial description, remains a neoplasm of uncertain histogenesis. The disease-defining molecular event characterizing the diagnosis of ASPS is the ASPSCR1-TFE3 fusion gene. Following identification of an index case of ASPS with a novel TFE3 fusion partner, we performed a retrospective review to determine whether this represents an isolated event. We identified two additional cases, for a total of three cases lacking ASPSCR1 partners. The average patient age was 46 years (range, 17-65); two patients were female. The sites of origin included the transverse colon, foot, and dura. Each case exhibited a histomorphology typical of ASPS, and immunohistochemistry was positive for TFE3 in all cases. Routine molecular testing of the index patient demonstrated a HNRNPH3-TFE3 gene fusion; the remaining cases were found to have DVL2-TFE3 or PRCC-TFE3 fusion products. The latter two fusions have previously been identified in renal cell carcinoma; to our knowledge, this is the first report of a HNRNPH3-TFE3 gene fusion. These findings highlight a heretofore underrecognized genetic diversity in ASPS, which appears to more broadly molecularly overlap with that of translocation-associated renal cell carcinoma and PEComa. These results have immediate implications in the diagnosis of ASPS since assays reliant upon ASPSCR1 may yield a false negative result. While these findings further understanding of the molecular pathogenesis of ASPS, issues related to the histogenesis of this unusual neoplasm remain unresolved.