Lewin J, et al. - In order to ascertain subsets of patients who harbour actionable mutations, experts sought to examine the utility of next generation sequencing (NGS) in undifferentiated pleomorphic sarcomas (UPS). This study did not find any impact of somatic mutation status on disease free or overall survival. In light of the small number of clinically relevant mutations, they did not support the routine use of targeted NGS panels outside of research protocols in UPS.

• By a pathologist specializing in sarcoma, patients diagnosed with UPS underwent pathological re-evaluation.
• From archived fresh frozen tissue samples, tumor DNA was isolated.
• By using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons), tumor DNA genotyped.
• This study delineated 95 patients initially classified with UPS.  
• In addition, following pathology re-review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N=44); UPS(N=18); and Others (N=27; including undifferentiated spindle cell sarcoma (N=15) and dedifferentiated liposarcoma (N=6)).
• From further analysis for other reasons, seven cases were excluded.
• A median age of 66 years (32-95), primarily with stage I-III disease (92%) and high grade (86%) lesions were demonstrated by baseline demographics of the finalized cohort (N=88).
• In 31 cases (35%), somatic mutations were identified (Total mutations=36: solitary mutation(n=27); two mutations(n=3); three mutations(n=1)).
• In TP53 (n=24), ATM(n=3) and PIK3CA (n=2), the most commonly mutations were identified.
• Mainly related to biomarkers of prediction of response, three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations.
• However, few had targetable driver mutations.