Details

Autor(en) / Beteiligte

• Le Loarer, François
• Cleven, Arjen H G
• Bouvier, Corinne
• Castex, Marie-Pierre
• Romagosa, Cleofe
• Moreau, Anne
• Salas, Sébastien
• Bonhomme, Benjamin
• Gomez-Brouchet, Anne
• Laurent, Camille
• Le Guellec, Sophie
• Audard, Virginie
• Giraud, Antoine
• Ramos-Oliver, Irma
• Cleton-Jansen, Anne-Marie
• Savci-Heijink, Dilara C
• Kroon, Herman M
• Baud, Jessica
• Pissaloux, Daniel
• Pierron, Gaëlle
• Sherwood, Anand
• Coindre, Jean Michel
• Bovée, Judith V M G
• Larousserie, Frédérique
• Tirode, Franck

Titel

A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation

Ist Teil von

• Modern pathology, 2020-03, Vol.33 (3), p.404-419

Ort / Verlag

United States: Elsevier Limited

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.