Sarcoma, NOS (SARCNOS)

Overview

Sarcoma, NOS (not otherwise specified) is a diagnostic category for sarcomas that cannot be further classified into a specific histologic subtype, classified under Soft Tissue Sarcoma in OncoTree (parent: SOFT_TISSUE). This category encompasses undifferentiated and unclassifiable spindle-cell, round-cell, or pleomorphic sarcomas.

Cohorts in the corpus

  • sarcoma_ucla_2024: represented in the 24-subtype UCLA sarcoma PDTO biobank. SARC0117, a metastatic undifferentiated spindle cell sarcoma (USS), is classified here and carried a PIK3CA hotspot mutation (reported as “H1074L”, canonical H1047L). (194 specimens from 126 patients, Feb 2018–May 2022). PMID:39305899

Recurrent alterations

  • PIK3CA: hotspot mutation (H1047L, rendered as “H1074L” in the manuscript) in SARC0117 (metastatic USS/SARCNOS) drove broad PI3K/mTOR sensitivity (alpelisib, apitolisib, copanlisib, BGT226, vistusertib). PMID:39305899
  • MET500 metastatic cohort: soft-tissue sarcoma (NOS) was the third most common lineage (42/500, 8.4%); a novel GREB1-NR4A3 activating fusion was identified in uterine leiomyosarcoma and a CIC-CITED1 fusion in undifferentiated high-grade sarcoma; NF1 was the most commonly fused tumor suppressor (n=18) across the cohort. PMID:28783718
  • TCGA Sarcoma working group profiled 206 adult soft tissue sarcomas across 6 histologies (LMS, DDLPS, UPS, MFS, SS, MPNST); pan-sarcoma mutation burden was low (mean 1.06 mut/Mb) with only 3 pan-cohort SMGs (TP53, ATRX, RB1), and complex karyotypes were SCNA-driven PMID:29100075

Subtypes

  • Undifferentiated pleomorphic sarcoma (UPS; overlaps with MFH)
  • Undifferentiated spindle cell sarcoma (USS)
  • Undifferentiated round cell sarcoma (when not meeting criteria for Ewing or other defined entities)

Therapeutic landscape

  • alpelisib: SARC0117 (metastatic USS/SARCNOS with PIK3CA H1047L) was among the strongest PI3K/mTOR responders in the UCLA PDTO screen; broad sensitivity across alpelisib, apitolisib, copanlisib, BGT226, vistusertib. PMID:39305899

Sources

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