Rhabdomyosarcoma with FUS re-arrangement: additional case in support of a novel subtype

Wong, Daniel; Vliet, Chris Van; Gaman, Andrew; Giardina, Tindaro; Amanuel, Benhur

doi:10.1016/j.pathol.2018.09.056

Cited by 30 publications

(53 citation statements)

References 10 publications

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“…Our data show that FET-TFCP2 rhabdomyosarcomas are associated with overall complex genetic profiles. This is in agreement with the features reported in one case characterized by genomic profiling (Affymetrix platform) which showed a tetraploid profile with numerous alterations, chromotripsis of 1p and 3p and homozygous deletion of CDKN2A (20). CDKN2A inactivation was indeed seen in all tested cases of our series (Supplementary Table 3).…”

Section: Discussionsupporting

confidence: 92%

“…No copy number alteration of ALK could be detected in both FET-TFCP2 tumors negative for ALK by immunohistochemistry. Interestingly, ALK deletion has been previously reported in one case of FUS-TFCP2 sarcoma: the sequencing data showed that the upregulation did not involve exons 1-16, therefore in keeping with our finding (20). Intriguingly, the expression of ALK has been shown with variable frequencies in other types of rhabdomyosarcomas, especially the alveolar subtype in up to 69% of cases (30,31) but its underlying biological mechanism remains elusive.…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2020

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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 to 86 years, including 5 pediatric cases. Tumors were located in 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 5 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 3 cases without underlying ALK fusion on break-apart FISH (n=5) nor next generation sequencing (n=14).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 12.8 to 90 and CDKN2A deletion was recurrent (n=9/10). 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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

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

et al. 2020

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“…A literature review of HNRMSs with TFCP2 fusions is provided in Table 2. To date (including the current study), 27 cases of HNRMS with TFCP2 fusions have been reported 5–14 . The tumours mostly affect young adults but may also occur in elderly patients.…”

Section: Discussionmentioning

confidence: 69%

“…Paediatric patients (defined as 21 years of age or younger) account for 37% of all cases. There is a slight male predominance, with a male/female ratio of 1.25:1 5–14 …”

Section: Discussionmentioning

confidence: 99%

“…It was initially recognised as a distinct pathological entity on the basis of its recurrent gene fusions, including TFCP2 fusions with either EWSR1 or FUS , and less commonly MEIS – NCOA2 fusions 5,6 . To date, <40 cases of intraosseous RMS with confirmed FUS / EWSR1 – TFCP2 or MEIS – NCOA2 fusions have been reported 5–14 . Whereas intraosseous RMSs with MEIS – NCOA2 fusions have been reported exclusively in the pelvic bones, RMSs with TFCP2 fusions show a striking predilection for a craniofacial intraosseous location, although large series are not yet available.…”

Section: Introductionmentioning

confidence: 99%

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Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases

Suurmeijer²,

Agaram

et al. 2021

Histopathology

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Aims Primary intraosseous rhabdomyosarcoma (RMS) is a rare entity defined by EWSR1/FUS–TFCP2 or, less commonly, MEIS1–NCOA2 fusions. The lesions often show a hybrid spindle and epithelioid phenotype, frequently coexpress myogenic markers, ALK, and cytokeratin, and show a striking propensity for the pelvic and craniofacial bones. The aim of this study was to investigate the clinicopathological and molecular features of 11 head and neck RMSs (HNRMSs) characterised by the genetic alterations described in intraosseous RMS. Methods and results The molecular abnormalities were analysed with fluorescence in‐situ hybridisation and/or targeted RNA/DNA sequencing. Seven cases had FUS–TFCP2 fusions, four had EWSR1–TFCP2 fusions, and none had MEIS1–NCOA2 fusions. All except one case were intraosseous, affecting the mandible (n = 4), maxilla (n = 3), and skull (n = 3). One case occurred in the superficial soft tissue of the neck. The median age was 29 years (range, 16–74 years), with an equal sex distribution. All tumours showed mixed epithelioid and spindle morphology. Immunohistochemical coexpression of desmin, myogenin, MyoD1, ALK, and cytokeratin was seen in most cases. An intragenic ALK deletion was seen in 43% of cases. Regional and distant spread were seen in three and four patients, respectively. Two patients died of their disease. Conclusions We herein present the largest series of HNRMSs with TFCP2 fusions to date. The findings show a strong predilection for the skeleton in young adults, although we also report an extraosseous case. The tumours are characterised by a distinctive spindle and epithelioid phenotype and a peculiar immunoprofile, with coexpression of myogenic markers, epithelial markers, and ALK. They are associated with a poor prognosis, including regional or distant spread and disease‐related death.

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TFCP2‐rearranged epithelioid and spindle cell rhabdomyosarcoma in the bladder: A rare case in an 8‐year‐old female child

Feng

Ding

et al. 2022

Pediatric Blood & Cancer

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Rhabdomyosarcoma with FUS re-arrangement: additional case in support of a novel subtype

Cited by 30 publications

References 10 publications

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

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

Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases

TFCP2‐rearranged epithelioid and spindle cell rhabdomyosarcoma in the bladder: A rare case in an 8‐year‐old female child

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