Deciphering the Genomic Landscape and Pharmacological Profile of Uncommon Entities of Adult Rhabdomyosarcomas

Abstract

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease.

A Rationale for the Activity of Bone Target Therapy and Tyrosine Kinase Inhibitor Combination in Giant Cell Tumor of Bone and Desmoplastic Fibroma: Translational Evidences

“…The online tool Primer-Blast provided by NCBI was used to design primers, spanning an exon-exon junction or flanking intron sequence/s to avoid genomic DNA contamination. The primers and probes sequences were as previously reported [ 30 , 31 , 32 ]. Taqman Universal PCR Master Mix (Applied Biosystems, Waltham, MA, USA) or SYBR Select Master Mix (Applied Biosystems, Waltham, MA, USA) were used for gene expression assay, with 400 nM final concentration of the corresponding forward and reverse primer (Sigma, Burlington, MA, USA) or Taqman probe, and 10 ng/μL final concentration of cDNA samples.…”

Case Report: Adult NTRK-Rearranged Spindle Cell Neoplasm: Early Tumor Shrinkage in a Case With Bone and Visceral Metastases Treated With Targeted Therapy

“…MSI plays a role in some tumor types as a prognostic and predictive biomarker of response to immunotherapy (32)(33)(34) and results from an impaired DNA mismatch repair (MMR) system, whose job is to recognize and repair damage to DNA. The results from studies on the involvement of MSI in the STS tumorigenesis are somewhat contradictory, highlighting the need for further investigation (35)(36)(37)(38). Our patient's tumor showed microsatellite stability, suggesting that this specific molecular mechanism was not involved in his disease.…”

Case Report: Primary Intraosseous Poorly Differentiated Synovial Sarcoma of the Femur

“…Almost all rhabdomyosarcoma samples show positive nuclear staining with antibodies to MyoD1 and/or myogenin, with nonrhabdomyosarcoma pediatric tumors being consistently negative ( 42 ). CD99, being negative in more than 50% of cases, is also not specific marker for RMS ( 43 , 44 ). Desmoplastic small round-cell tumors (DSRCTs) possess a distinctive, diagnostically significant immunophenotype, showing coexpression of epithelial (keratin), mesenchymal (desmin, vimentin), and neural (NSE) markers.…”