Molecular features of undifferentiated sarcoma of soft tissue and carcinoma.

Abstract

e23519 Background: Both undifferentiated sarcoma of soft tissue and undifferentiated carcinomas can arise in multiple tissue and are with an aggressive clinical course. While undifferentiated sarcomas that remain a diagnosis of exclusion and show extreme genomic complexity, less is known about undifferentiated carcinoma. Methods: Sixty-two patients diagnosed as undifferentiated sarcoma (n = 36, 10 bone/limbs, 9 abdomen, 9 pelvis, and 8 chest/intrathoracic) or carcinoma (n = 26, excluding undifferentiated carcinoma of nasopharynx and thyroid, 15 chest/intrathoracic, 8 abdomen, and 3 pelvis) were recruited in the study. Mutational analysis was performed by next-generation sequencing of 1021 tumor related genes, which enabled analysis of TMB and MSI as well. PD-L1 expression data was available in 24 patients. Results: Fifty-eight patients (93.5%, 58/62) had at least 1 mutation identified and 542 SNV, 115 CNV and 5 fusions were identified in total in the 62 patients. The top 5 mutant genes were TP53 (56.5%, 35/62), TERT (11.3 %, 7/62), SMARCA4 (9.7%, 6/62), LRP1B (9.7%, 6/62), and MLL2 (9.7%, 6/62). Interestingly, mutation in TP53 was more common in undifferentiated carcinoma (73.08%, 19/26) than sarcoma (44.44%, 16/36, p = 0.0377). Two ERBB2 CNV and 1 KIF5B-RET fusion were identified in 2 gastric carcinoma and 1 lung large cell carcinoma. However, no carcinoma but 2 sarcoma (1 polymorphic undifferentiated sarcoma in the limb and 1 undifferentiated small round cell sarcoma in the lung) showed MSI-H, with TMB as high as 22.08 and 65.28 respectively, while the median TMB was 3.84 mutations/Mb. Among the 24 patients with PD-L1 data, 16 were > 1%, and 5 were > 50%, with no significant difference between undifferentiated carcinoma and sarcoma. Conclusions: In spite of the genome complexity in undifferentiated sarcoma of soft tissue and carcinoma, there was limited actionable mutations in these two aggressive tumors. However, immunotherapy should be considered since over half of these patients were PD-L1 positive and nearly a quarter of them had high PD-L1 expression.