Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors Journal Article
| Authors: | Dickson, B. C.; Chung, C. T. S.; Hurlbut, D. J.; Marrano, P.; Shago, M.; Sung, Y. S.; Swanson, D.; Zhang, L.; Antonescu, C. R. |
| Article Title: | Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors |
| Abstract: | 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. © 2019 Wiley Periodicals, Inc. |
| Keywords: | immunohistochemistry; adolescent; adult; clinical article; aged; middle aged; case report; tumor localization; genetic variability; retrospective study; age; fluorescence in situ hybridization; fusion gene; dura mater; rna sequence; alveolar soft part sarcoma; fusion; foot; tfe3; aspscr1; transverse colon; prcc; human; male; female; priority journal; article; aspscr1 tfe3 fusion gene; prcc tfe3 gene; dvl2; hnrnph3; dvl2 tfe3 gene; hnrnph3 tfe3 fusion gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 59 |
| Issue: | 1 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2020-01-01 |
| Start Page: | 23 |
| End Page: | 29 |
| Language: | English |
| DOI: | 10.1002/gcc.22803 |
| PUBMED: | 31433528 |
| PROVIDER: | scopus |
| PMCID: | PMC7057290 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 December 2019 -- Source: Scopus |
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