Congenital undifferentiated sarcoma associated to BCOR-CCNB3 gene fusion

Alfaro-Cervelló, Clara; Andrade-Gamarra, Veronica; Nieto, Gema; Navarro, Lara; Martín-Vañó, Susana; Torre, Juan Pablo García de la; Caamaño, María Bengoa; Mauriño, Ma Luisa García; Noguera, Rosa; Navarro, Samuel

doi:10.1016/j.prp.2017.07.012

Cited by 8 publications

(5 citation statements)

References 13 publications

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“… 5 - 8 , 11 Again, because of the age of presentation, one could be concerned about an inherited cancer syndrome. Alfaro-Cervello et al 12 published a case report of a congenital undifferentiated sarcoma with BCOR - CCNB3 fusion possibly similar to our patient case. This congenital tumor also harbored a SMARCB1 / INI1 gene deletion common to malignant rhabdoid tumor, epithelioid sarcomas, and epithelioid malignant peripheral nerve sheath tumor that also, when found germline, is known to cause rhabdoid tumor predisposition syndrome.…”

Section: Discussionsupporting

confidence: 84%

“…This congenital tumor also harbored a SMARCB1 / INI1 gene deletion common to malignant rhabdoid tumor, epithelioid sarcomas, and epithelioid malignant peripheral nerve sheath tumor that also, when found germline, is known to cause rhabdoid tumor predisposition syndrome. 12 - 16 In the case reported by Alfaro-Cervello et al, 12 INI1 germline analysis was not performed. Our patient’s tumor had functionally intact INI1 , which precludes an effective comparison.…”

Section: Discussionmentioning

confidence: 97%

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Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma With BCOR-CCNB3 Fusion and Germline CDKN2B Variant

Tramontana

Marshall

Helvie

et al. 2020

JCO Precision Oncology

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 97%

Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma With BCOR-CCNB3 Fusion and Germline CDKN2B Variant

Tramontana

Marshall

Helvie

et al. 2020

JCO Precision Oncology

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“…Forty-one publications met criteria for inclusion 2,4,5,7–46. These publications described 190 patients with BCOR altered sarcomas arising from the soft tissues and organs (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Soft Tissue and Visceral Organ Sarcomas With BCOR Alterations

Whittle

Fetzko

Roy

et al. 2022

Journal of Pediatric Hematology/Oncology

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Sarcomas with BCOR alteration are a heterogenous group characterized by changes including internal tandem duplications (ITDs) and recurring fusions with CCNB3, ZC3H7B, and other rare partners. With widespread genomic testing, these alterations are now associated with histologies such as Ewing-like sarcoma (BCOR:: CCNB3), high-grade endometrial stromal sarcoma (ZC3H7B:: BCOR), and clear cell sarcoma of kidney (BCOR-ITD). BCOR altered sarcomas of soft tissues and organs were identified through PubMed using keywords "Sarcoma (AND) BCOR" from 2005 through October 2021. Summary statistics and outcome data were calculated using STATA v12.1. Forty-one publications described 190 patients with BCOR altered soft tissue or organ sarcomas. BCOR-ITD was most common, followed by BCOR::CCNB3, ZC3H7B:: BCOR. BCOR-ITD tumors occurred mainly in infants, BCOR:: CCNB3 commonly occurred in adolescent young adults, and ZC3H7B::BCOR only in adults. The most common site for BCOR:: CCNB3 fused tumors was extremity, BCOR-ITD kidney and ZC3H7B::BCOR uterus. Metastasis was rare in patients with BCOR::CCNB3. While most underwent resection and chemotherapy, few received radiation. Median follow-up of survivors was 24 months. Five year overall survival for patients with BCOR::CCNB3 fusions was 68% (95% confidence interval [CI]: 46%-83%). Patients with BCOR-ITD and ZC3H7B::BCOR had worse prognoses with 5 years overall survival of 35% (95% CI: 15%-56%) and 41% (95% CI: 11%-71%), respectively, demonstrating need for collaborative efforts identifying optimal treatments to improve outcomes.

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“…This suggests that higher expressions of EGFR, EPHA5, and BRINP3 are associated with a better response to PEG~TLZ+TMZ therapy in MRTs, while higher levels of FOXP1 levels are linked to drug resistance. Additionally, there were genes like CADM1 , CCNB3 , CDH6 , CDH9 , CLDN10 , EFNB1 , EFNB2 , FGF3 , FGF4 , FGF19 , KIT, and PIK3AP1 that had high expressions exclusively in the WT-16 xenograft—the model with an MCR response and a relapsed MRT model ( Table 4 ; Supplemental Figure S6B ) [ 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. This suggests that transcriptional patterns could help identify which MRTs might respond better to this specific treatment regimen.…”

Section: Resultsmentioning

confidence: 99%

Synergistic Antitumor Activity of Talazoparib and Temozolomide in Malignant Rhabdoid Tumors

Mironova,

Molinas,

Pozo

et al. 2024

Cancers

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Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1 gene (occasionally SMARCA4)—a pivotal component of the SWI/SNF chromatin remodeling complex—is homozygously deleted, although the precise etiology of these tumors remains unknown. While young patients with localized MRT generally show improved outcomes, especially those who are older and have early-stage disease, the overall prognosis remains poor despite optimal standard treatments. This highlights the urgent need for more effective treatment strategies. We investigated the antitumor activity of a PARP1 inhibitor (talazoparib, TLZ) combined with a DNA alkylating agent (temozolomide, TMZ) in MRT xenograft models. PARP1 is a widely targeted molecule in cancer treatment and, beyond its role in DNA repair, it participates in transcriptional regulation by recruiting chromatin remodeling complexes to modulate DNA accessibility for RNA polymerases. To widen the therapeutic window of the drug combination, we employed PEGylated TLZ (PEG~TLZ), which has been reported to reduce systemic toxicity through slow drug release. Remarkably, our findings indicate that five out of six MRT xenografts exhibited an objective response to PEG~TLZ+TMZ therapy. Significantly, the loss of SMARCB1 was found to confer a protective effect, correlating with higher expression levels of DNA damage and repair proteins in SMARCB1-deficient MRT cells. Additionally, we identified MGMT as a potential biomarker indicative of in vivo MRT response to PEG~TLZ+TMZ therapy. Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response.

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Congenital undifferentiated sarcoma associated to BCOR-CCNB3 gene fusion

Cited by 8 publications

References 13 publications

Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma With BCOR-CCNB3 Fusion and Germline CDKN2B Variant

Sustained Complete Response to Palbociclib in a Refractory Pediatric Sarcoma With BCOR-CCNB3 Fusion and Germline CDKN2B Variant

Soft Tissue and Visceral Organ Sarcomas With BCOR Alterations

Synergistic Antitumor Activity of Talazoparib and Temozolomide in Malignant Rhabdoid Tumors

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