Novel MEIS1-NCOA2 Gene Fusions Define a Distinct Primitive Spindle Cell Sarcoma of the Kidney

Argani, Pedram; Reuter, Victor E.; Kapur, Payal; Brown, James E.; Sung, Yun Shao; Zhang, Lei; Williamson, Richard; Francis, Glen; Sommerville, Scott; Swanson, David; Dickson, Brendan C.; Antonescu, Cristina R.

doi:10.1097/pas.0000000000001140

Cited by 38 publications

(57 citation statements)

References 50 publications

(47 reference statements)

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“…The histologic appearance was somewhat reminiscent to congenital/ infantile spindle cell rhabdomyosarcoma or to other undifferentiated spindle cell sarcomas, such as monophasic synovial sarcomas, BCOR-family of tumors, etc. MEIS1-NCOA2 gene fusion was recently reported by our group in two undifferentiated spindle cell sarcomas of the kidney (12), which occurred in a 72 year-old woman and a 21 year-old man. One of the cases in our study (Case 2) showed tumor cells arranged in a whorled pattern, similar to the renal case# 1 from the study by Argani et al (12).…”

Section: Discussionmentioning

confidence: 63%

“…MEIS1-NCOA2 gene fusion was recently reported by our group in two undifferentiated spindle cell sarcomas of the kidney (12), which occurred in a 72 year-old woman and a 21 year-old man. One of the cases in our study (Case 2) showed tumor cells arranged in a whorled pattern, similar to the renal case# 1 from the study by Argani et al (12). By RNA sequencing, the fusion transcripts in the kidney tumors were slightly different, including MEIS1 exon 7 fused to NCOA2 exon 13/14, while the current case showed MEIS1 exon 6 fused to NCOA2 exon 12.…”

Section: Discussionmentioning

confidence: 63%

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Expanding the Spectrum of Intraosseous Rhabdomyosarcoma

Agaram

Zhang

Sung

et al. 2019

American Journal of Surgical Pathology

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Primary intraosseous rhabdomyosarcomas are extremely rare. Recently two studies reported 4 cases of primary intraosseous rhabdomyosarcoma with EWSR1/FUS-TFCP2 gene fusions, associated with somewhat conflicting histologic features, ranging from spindle to epithelioid. In this study we sought to further investigate the pathologic and molecular abnormalities of a larger group of intraosseous rhabdomyosarcomas by a combined approach using targeted RNA sequencing analysis and fluorescence in-situ hybridization (FISH). We identified 7 cases, 3 males and 4 females, all in young adults, age range 20-39 years (median 27 years). Three cases involved the pelvis, 2 involved the femur and 1 each involved the maxilla and the skull. Molecular studies identified recurrent gene fusions in all 7 cases tested, including: a novel MEIS1-NCOA2 fusion in 2 cases, EWSR1-TFCP2 in 3 cases and FUS-TFCP2 gene fusions in 1 case. One case showed a FUS gene rearrangement, without a TFCP2 gene abnormality by FISH. The MEIS1-NCOA2 positive cases were characterized by a more primitive and fascicular spindle cell appearance, while the EWSR1/FUS rearranged tumors had a hybrid spindle and epithelioid phenotype, with more abundant eosinophilic cytoplasm and mild nuclear pleomorphism. Immunohistochemically, all tumors were positive for desmin and myogenin (focal). In addition, 4 tumors with TFCP2 associated gene fusions also co-expressed ALK and Cytokeratin. In conclusion, our results suggest a high incidence of gene fusions in primary rhabdomyosarcomas of bone, with two molecular subsets emerging, defined by either MEIS1-NCOA2 or EWSR1/FUS-TFCP2 fusions, showing distinct morphology and immunophenotype. Additional studies with larger numbers of cases and

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 63%

Expanding the Spectrum of Intraosseous Rhabdomyosarcoma

Agaram

Zhang

Sung

et al. 2019

American Journal of Surgical Pathology

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“…Emerging translocation‐associated renal soft tissue tumors have been recently described, including two tumors with MEIS1‐NCOA2 fusion that displayed distinctive nodular spindle cell proliferations, variable entrapped cystic renal tubules, and aggressive histologic features 2 . In addition, two cases of renal BCOR‐CCNB3 fusion‐associated sarcomas were reported in pediatric patients, showing cellular spindle cell morphology, cystic change, and purported overlap with clear cell sarcoma of kidney 1 .…”

Section: Discussionmentioning

confidence: 99%

“…A remarkable variety of both established and emerging fusion‐associated soft tissue tumors has been documented within the kidney, including synovial sarcoma, Ewing sarcoma, solitary fibrous tumor, congenital mesoblastic nephroma, clear cell sarcoma of kidney, and recently described MEIS1‐NCOA2 and BCOR‐CCNB3 ‐associated tumors 1‐3 . In addition, MiTF family translocation‐associated renal cell carcinomas (typically Xp11.2 TFE3 or t[6;11] TFEB rearrangements) represent a group of fusion‐associated epithelial malignancies.…”

Section: Introductionmentioning

confidence: 99%

Primary myxoid and epithelioid mesenchymal tumor of the kidney with a novel GLI1‐FOXO4 fusion

Pettus

Kerr

Stan

et al. 2020

Genes Chromosomes & Cancer

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To our knowledge, we describe the first mesenchymal tumor with a novel GLI1‐FOXO4 fusion gene. This well‐circumscribed kidney tumor displayed variably myxoid and epithelioid histologic features with a focally nodular growth pattern. The tumor cells showed bland, round to ovoid nuclei, with no overt high‐grade features. The tumor showed focal immunopositivity for smooth muscle actin and Melan‐A, which raised the possibility of a relationship with a perivascular epithelioid cell tumor. The clinical and morphologic features appear distinct from other reported neoplasms harboring GLI1 or FOXO4 gene rearrangements. The patient underwent radical nephrectomy and is without evidence of disease during a relatively short clinical follow‐up period. However, the features of this tumor likely warrant long‐term follow‐up to monitor for the possibility of a late recurrence or metastasis. In addition to reporting this novel fusion‐positive tumor, we also provide a brief review of GLI1 and FOXO4 gene functions in both normal and neoplastic contexts.

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“…Members of the nuclear receptor coactivator (NCOA) gene family interact, in a ligand‐dependent manner, with nuclear receptors, and other transcription factors, to enhance transcriptional activation . In addition to soft tissue angiofibroma, fusions involving NCOA2 have been identified in mesenchymal chondrosarcoma, variants of rhabdomyosarcoma, uterine adenosarcoma, uterine tumor resembling ovarian sex cord tumor, spindle cell sarcoma of kidney, and biphenotypic sinonasal sarcoma . There is significant homology amongst members of the NCOA family; unsurprisingly, fusions involving other NCOA family members— NCOA1 and NCOA3 —have likewise been implicated in many of the same, or related, mesenchymal tumors.…”

Section: Discussionmentioning

confidence: 99%

PRRX‐NCOA1/2 rearrangement characterizes a distinctive fibroblastic neoplasm

Lacambra

Weinreb

Demicco

et al. 2019

Genes Chromosomes & Cancer

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Fibroblastic/myofibroblastic neoplasms represent a broad, and occasionally diagnostically challenging, category of soft tissue neoplasms. A subset of these tumors defy conventional classification. However, with the advent of next‐generation sequencing, the identification of disease‐defining molecular alterations is gradually improving their subclassification. Following identification of two index cases of a distinctive fibroblastic neoplasm with a fusion gene involving PRRX1 and NCOA1, we performed a retrospective review to further characterize this entity. We identified two additional cases, including one with a fusion between PRRX1 and NCOA2. The average patient age was 38 years, and three patients were female. Two tumors occurred on the neck, and the others involved the groin and thigh. Tumors were centered in the subcutis and ranged from 2.3 to 14.0 cm (average 5.8 cm). Morphologically, they were predominantly hypocellular, with focal hypercellularity. They were composed of monomorphic spindle‐stellate cells with a vague fascicular pattern. The nuclei were bland with only rare mitotic activity, and occasional multinucleation. The intervening stroma was typically abundant and ranged from myxoid to collagenous, with frequent rope‐like collagen bundles. Three of the cases had a prominent vasculature ranging from numerous small curvilinear vessels to ectatic and branching staghorn‐like vessels. Immunohistochemistry was negative for desmin, smooth muscle actin, S100, CD34, keratin, and epithelial membrane antigen. Each of the patients was treated by simple excision and none of the tumors were associated with local recurrence or metastasis. Based on their unique morphological and molecular attributes, we believe this represents a novel fibroblastic tumor for which we have tentatively proposed the name “PRRX‐NCOAx‐rearranged fibroblastic tumor.”

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Novel MEIS1-NCOA2 Gene Fusions Define a Distinct Primitive Spindle Cell Sarcoma of the Kidney

Cited by 38 publications

References 50 publications

Expanding the Spectrum of Intraosseous Rhabdomyosarcoma

Expanding the Spectrum of Intraosseous Rhabdomyosarcoma

Primary myxoid and epithelioid mesenchymal tumor of the kidney with a novel GLI1‐FOXO4 fusion

PRRX‐NCOA1/2 rearrangement characterizes a distinctive fibroblastic neoplasm

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