(P 56) COMPARISON OF PATHOGENIC AND LIKELY PATHOGENIC VARIANTS DISTINCT FROM SPECIFIC DRIVERS IN DIFFERENT SARCOMA GROUPS

Objective: To comparatively describe pathogenic and likely pathogenic variants (PLPVs) distinct from specific drivers in sarcomas by relevant groups.

Methods: We retrospectively reviewed NGS reports of patients with sarcomas in our Center. Sarcomas were divided into three groups: translocation-related sarcomas (TRS), translocation-unrelated sarcomas with activating mutations (AM), or without them(WAM).

Results: Eighty-five patients with a median age of 38 years were included. In the TRS group, PLPVs different from the specific translocation were found in 8/27 (29.6%) of patients. STAG2 (5/27), TP53 (2/27), and APC (2/27) were the most commonly mutated genes. DDR, WNT, and Epigenetic regulation were the most commonly involved pathways. In the AM group, 7 secondary mutations were found in 13 patients (53.8%), all of them in 11 Gastrointestinal Stromal Tumor patients. The main pathway involved was the MYC, linked to MGA mutations. In the WAM group, in 9 patients with Desmoid fibromatosis a total of 10 PLPVs different from CTNNB1 or APC were identified across 7 patients. In the 36 other WAM sarcomas, the PLPVs were found in 50% of patients: being ATRX (8.3%) and TP53 (5.5%) the two most common. Epigenetic regulation, RTK-RAS, and DDR were the most commonly altered pathways.

Conclusion: In sarcomas with specific drivers, additional PLPVs are common. Some of them have a strong sarcoma-type specificity, while others are shared between sarcoma groups, as well as the main signaling pathways they alter. The effectiveness of therapeutic actionability on these alterations should be studied.

Comparison of pathogenic variants distinct from from the specific drivers in different sarcoma types.