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Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors
Author(s) -
Dickson Brendan C.,
Chung Catherine T.S.,
Hurlbut David J.,
Marrano Paula,
Shago Mary,
Sung YunShao,
Swanson David,
Zhang Lei,
Antonescu Cristina R.
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22803
Subject(s) - histogenesis , alveolar soft part sarcoma , tfe3 , fusion gene , malignancy , biology , gene rearrangement , pathology , sarcoma , cabozantinib , renal cell carcinoma , medicine , genetics , gene , immunohistochemistry , gene expression , promoter
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.