Vulvar angiomyofibroblastoma is molecularly defined by recurrent MTG1-CYP2E1 fusions.

TitleVulvar angiomyofibroblastoma is molecularly defined by recurrent MTG1-CYP2E1 fusions.
Publication TypeJournal Article
Year of Publication2022
AuthorsBoyraz B, Tajiri R, Alwaqfi RR, Paula ADa Cruz, Ye Q, G Nielsen P, Hung YP, Oliva E, Weigelt B, Hisaoka M, Watkins JC
Date Published2022 Dec
KeywordsAdult, Cytochrome P-450 CYP2E1, Female, Humans, Middle Aged, Recurrence, Sarcoma, Sequence Analysis, RNA, Soft Tissue Neoplasms, Vulvar Neoplasms

Angiomyofibroblastoma (AMF), a rare benign vulvovaginal mesenchymal tumour, poses a diagnostic challenge due to histologic and immunohistochemical overlap with other vulvar mesenchymal tumours. Recently, MTG1-CYP2E1 fusion transcripts were reported in 5/5 AMFs; no other genetic alterations have been described to date. Herein, we sought to investigate the frequency of the MTG1-CYP2E1 fusion and the presence of other potential genetic alterations in a cohort of AMFs (n = 7, patient age range: 28-49 years). Tumours demonstrated classic morphologic features including alternating hypo/hypercellular areas, capillary channels surrounded by epithelioid/spindled tumour cells, and variable amounts of mature adipose tissue. reverse transcription-polymerase chain reaction (RT-PCR) for MTG1-CYP2E1 fusion, performed in all seven cases, showed the fusion transcript in five of six cases (one case with technical failure). Two tumours, including the one lacking the fusion, were subjected to targeted next-generation sequencing (104 genes) and a sarcoma fusion assay (28 genes); the fusion negative AMF also underwent RNA sequencing. No additional mutations, copy number alterations, or fusion genes were identified with the assays employed. We conclude that the majority of AMFs harbour recurrent MTG1-CYP2E1 fusion transcripts and identification of this fusion may aid in the diagnosis.

Alternate JournalHistopathology
PubMed ID36177509
PubMed Central IDPMC10335785
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
P50 CA247749 / CA / NCI NIH HHS / United States
Related Faculty: 
Baris Boyraz, M.D., Ph.D.

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