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| Home > Publications database > Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor. |
| Home > Publications database > Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor. |
| Journal Article | DKFZ-2026-00838 |
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2026
Springer Nature
[London]
Abstract: Desmoplastic small round cell tumor (DSRCT) is an ultra-rare sarcoma with limited treatment options. Here, we show that comprehensive molecular profiling informs diagnosis and individualized therapy in this disease. We report the results of whole-genome/exome, transcriptome, and DNA methylome analyses performed in 30 refractory DSRCT patients, complemented by (phospho)proteomic profiling in nine, within a nationwide precision oncology program. In eight patients (27%), DSRCT was diagnosed only after molecular profiling. Although DSRCTs have 'quiet' genomes, 28 patients (93%) received 107 molecular-based management recommendations, including assessment of clinical trial eligibility in 17 (57%). Most recommendations are informed by overexpression of tyrosine kinases, SSTR3/5, and CLDN6, detected in 45%, 33%, and 20% of cases, respectively. Thirteen patients (46%) received recommended therapies, yielding disease control in eight (62%), including three long-lasting responses to pazopanib and trastuzumab deruxtecan, the latter administered based on ERBB2 overexpression in the absence of aberrant ERBB2 kinase activation. These findings demonstrate that multi-omics profiling provides clinically actionable insights for DSRCT management.
Keyword(s): Humans (MeSH) ; Desmoplastic Small Round Cell Tumor: genetics (MeSH) ; Desmoplastic Small Round Cell Tumor: diagnosis (MeSH) ; Desmoplastic Small Round Cell Tumor: drug therapy (MeSH) ; Desmoplastic Small Round Cell Tumor: metabolism (MeSH) ; Desmoplastic Small Round Cell Tumor: therapy (MeSH) ; Female (MeSH) ; Male (MeSH) ; Adult (MeSH) ; Middle Aged (MeSH) ; Young Adult (MeSH) ; Adolescent (MeSH) ; Pyrimidines: therapeutic use (MeSH) ; Molecular Targeted Therapy (MeSH) ; DNA Methylation (MeSH) ; Proteomics: methods (MeSH) ; Gene Expression Profiling (MeSH) ; Sulfonamides: therapeutic use (MeSH) ; Transcriptome (MeSH) ; Trastuzumab: therapeutic use (MeSH) ; Receptors, Somatostatin: genetics (MeSH) ; Receptors, Somatostatin: metabolism (MeSH) ; Erb-b2 Receptor Tyrosine Kinases: metabolism (MeSH) ; Erb-b2 Receptor Tyrosine Kinases: genetics (MeSH) ; Indazoles (MeSH) ; Pyrimidines ; pazopanib ; Sulfonamides ; Trastuzumab ; Receptors, Somatostatin ; Erb-b2 Receptor Tyrosine Kinases ; Indazoles
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