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Updated: Jan 2, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Recurrent and novel USP6 fusions in cranial fasciitis identified by targeted RNA sequencing
Vera A Paulson1,2, Ivan A Stojanov3, Jay K Wasman4
1Department of Pathology, Boston Children's Hospital, Boston, MA, USA.
Abstract:
Cranial fasciitis is a benign myofibroproliferative lesion of the scalp and underlying bones typically occurring in the pediatric population. Histologically, it is characterized by loose fascicles of stellate cells in a fibromyxoid background, findings similar to those described in the closely related variant nodular fasciitis. Previously characterized as a reactive process, the identification of USP6 translocations in over 90% of nodular fasciitis cases prompted their reclassification as a clonal neoplastic process. Unlike nodular fasciitis, the molecular underpinnings of cranial fasciitis are less clear. While a subset of cranial fasciitis has been associated with Wnt/β-catenin pathway dysregulation, recent case reports suggest that this entity may also harbor USP6 fusions, a finding we sought to further investigate. We identified fifteen archival cases of cranial fasciitis, five females and ten males ranging in age from 3 months to 9 years (median 11 months), composed of formalin-fixed paraffin-embedded and fresh frozen tissues (11 and 4 cases respectively). Samples were evaluated on an RNA-based targeted sequencing panel targeting genes recurrently rearranged in neoplasia, including USP6. Five of fifteen cases (33%) were positive for USP6 rearrangements predicted to result in the fusion of the entire USP6 coding region to the promoter of the 5' partner, (three of which were novel): two SERPINH1-USP6 (novel) and one each of COL3A1-USP6 (novel), SPARC-USP6, and MYH9-USP6. These results demonstrate the recurrent nature of USP6 rearrangements in cranial fasciitis, and highlight the success of targeted RNA sequencing in identifying known and novel fusion partners. The identification of USP6 promoter-swapping rearrangements is helpful in understanding the underlying biology of cranial fasciitis, and reinforces its biologic relationship to nodular fasciitis. Targeted RNA sequencing is a helpful tool in diagnosing this pseudosarcomatous lesion.
Insights
Cranial fasciitis, a pediatric scalp lesion, is now understood to frequently involve USP6 rearrangements, similar to nodular fasciitis. Targeted RNA sequencing successfully identified these genetic alterations, aiding diagnosis.
Area of Science:
- Oncology
- Genetics
- Pediatric Pathology
Background:
- Cranial fasciitis is a benign myofibroproliferative lesion of the pediatric scalp.
- It shares histological similarities with nodular fasciitis, a neoplastic process characterized by USP6 translocations.
- The molecular basis of cranial fasciitis remains less understood compared to nodular fasciitis.
Purpose of the Study:
- To investigate the presence and spectrum of USP6 rearrangements in cranial fasciitis.
- To determine if cranial fasciitis shares the USP6 fusion profile seen in nodular fasciitis.
- To evaluate the utility of targeted RNA sequencing in identifying USP6 fusions in cranial fasciitis.
Main Methods:
- Archival samples from fifteen cranial fasciitis cases were analyzed.
- A targeted RNA sequencing panel was employed to detect gene rearrangements, including USP6.
- USP6 rearrangements were identified and characterized, including novel fusion partners.
Main Results:
- USP6 rearrangements were detected in five out of fifteen (33%) cranial fasciitis cases.
- Three novel USP6 fusions were identified: SERPINH1-USP6 (two cases) and COL3A1-USP6 (one case).
- Other identified USP6 fusions included SPARC-USP6 and MYH9-USP6.
Conclusions:
- USP6 rearrangements are recurrent in cranial fasciitis, supporting its classification as a neoplastic process.
- The findings reinforce the biological relationship between cranial fasciitis and nodular fasciitis.
- Targeted RNA sequencing is an effective tool for diagnosing cranial fasciitis by identifying USP6 alterations.
