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Updated: Aug 29, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
ALK overexpression without rearrangement widely exists in EWSR1/FUS-rearranged soft tissue tumours
1Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Aims:
Anaplastic lymphoma kinase (ALK) is implicated in ALK fusion-positive non-small cell lung cancer and inflammatory myofibroblastic tumours. Based on prior studies and our observations, ALK overexpression appears to be associated with FET (FUS/EWSR1/TAF15) family rearrangements (EWSR1 and FUS).
Methods:
In this study, we analysed 119 FET-rearranged tumours spanning 20 tumour types. Using ALK D5F3 immunohistochemistry (IHC), ALK overexpression was defined as positive only for scores of 2+ or 3+. Cases with ALK overexpression by IHC were further confirmed to lack ALK gene rearrangements.
Results:
Among the cases, 28.6% (34/119) demonstrated ALK overexpression (≥2+). 9 disease types displayed ALK overexpression (≥2+), including soft tissue sarcomas and salivary gland carcinomas. Notably, Ewing sarcoma had the highest ALK overexpression rate (51%, 22/43). Both analysed clear cell sarcoma-like tumour of the gastrointestinal tract (GNET) cases (2/2) were strongly positive (3+), while extraskeletal myxoid chondrosarcoma exhibited a high overexpression rate (50%, 2/4). Additionally, angiomatoid fibrous histiocytoma showed moderate staining (75%, 3/4, 2+). The other tumours with ALK overexpression were pulmonary myoepithelial carcinoma (1/1), EWSR1-rearranged rhabdomyosarcoma (1/1), desmoplastic small round cell tumour (25%, 1/4), clear cell sarcoma of soft tissue (7.7%, 1/13) and myxoid liposarcoma (6.7%, 1/15). ALK overexpression (IHC≥2+) occurred in both EWSR1-rearranged and FUS-rearranged tumours. Among fusion partners, FLI1-rearranged cases had the strongest ALK overexpression (70%, 7/10).
Conclusions:
Our findings demonstrate that ALK overexpression is frequent in FET-rearranged tumours, warranting caution to avoid misdiagnosis, while also presenting potential therapeutic opportunities.
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