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Response of BRAF-mutated spindle cell sarcoma to BRAF/MEK inhibitors

“This is the first report of spindle cell sarcoma BRAF V600E/S607T double-mutated, responding to a combination of B-Raf and MEK inhibitors.”

Peer-Reviewed Publication

Impact Journals LLC

Rapid but nondurable response of a BRAF exon 15 double-mutated spindle cell sarcoma to a combination of BRAF and MEK inhibitors

image: 

Figure 2: Morphological and genetic findings.
(A, B) Representative histological images, H&E, ×50 (A) and ×200 (B), showing short fascicles of spindle-shaped tumor cells with large ovoid nuclei, fibrous stroma with diffuse focal myxomatosis, small adipose clusters and signs of perivascular lymphoid infiltration. (C, D) Two closely spaced missense mutations identified in BRAF exon 15: (C) Schematic representation of B-Raf protein structure (SwissModel) with amino acid substitutions at positions 600 and 607 of the polypeptide shown in red and orange, respectively; (D) an IGV screenshot demonstrating BRAF mutations c.1799T>A p.V600E and c.1819T>A; p.S607T in cis-position.

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Credit: 2024 Sinichenkova et al.

“This is the first report of spindle cell sarcoma BRAF V600E/S607T double-mutated, responding to a combination of B-Raf and MEK inhibitors.”

BUFFALO, NY- August 14, 2024 – A new case report was published in Oncotarget's Volume 15 on July 17, 2024, entitled, “Rapid but nondurable response of a BRAF exon 15 double-mutated spindle cell sarcoma to a combination of BRAF and MEK inhibitors.”

As noted in the introduction of the Abstract, the BRAF V600E substitution predicts a cancer's sensitivity to BRAF inhibitor therapy, though the mutation is rarely found in soft-tissue sarcomas.

Researchers Kseniya Sinichenkova, Iliya Sidorov, Nataliya Kriventsova, Dmitriy Konovalov, Ruslan Abasov, Nataliya Usman, Alexander Karachunskiy, Galina Novichkova, Dmitriy Litvinov, and Alexander Druy from the Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology (Ministry of Healthcare of Russian Federation) and the Research Institute of Medical Cell Technologies in Yekaterinburg, Russia, describe a case of undifferentiated spindle cell sarcoma that exhibited primary insensitivity to standard chemotherapy and a pronounced but non-sustained response to BRAF/MEK inhibitors at recurrence.

The case presentation involved a 13-year-old girl that was diagnosed with low-grade spindle cell sarcoma of pelvic localization, BRAF exon 15 double-mutated: c.1799T>A p.V600E and c.1819T>A p.S607T in cis-position.

“This is the first report of spindle cell sarcoma BRAF V600E/S607T double-mutated, responding to a combination of B-Raf and MEK inhibitors.”

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28606

Correspondence to: Kseniya Sinichenkova - ksinichenkova@gmail.com

Keywords: undifferentiated sarcoma, BRAF V600E mutation, low grade spindle cell sarcoma, abdominal cocoon

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