(P 184) MTAP IN GASTROINTESTINAL STROMAL TUMOR (GIST): RATE OF MTAP LOSS AND CONCORDANCE BETWEEN GENOMIC SEQUENCING AND IMMUNOHISTOCHEMISTRY

Objective: GIST harboring CDKN2A homozygous deletion (del) have poorer prognosis. In solid tumors with CDKN2A del, co-deletion of the neighboring gene MTAP is common and actionable with PRMT5 inhibitors (PRMT5i). This study evaluates the rate of MTAP loss in GIST and the concordance between targeted exome sequencing (TES) and IHC.

Methods: Two tissue microarrays (TMAs) containing both primary and metastatic (met) GIST surgical specimens were stained for MTAP (Abnova monoclonal antibody clone 2G4). To evaluate IHC and TES concordance, a separate cohort with available research TES (Oncopanel) showing MTAP del or CDKN2A del was formed and clinically annotated. MTAP status was recorded as wild type (WT), single copy loss (SCL), or del. MTAP IHC was performed on the profiled tissue and additional specimens, if available.

Results: The 2 TMAs included primary tumors and mets and revealed a similar rate of MTAP loss in primary tumors (12/58, 21%) and mets (4/16, 25%). MTAP loss was enriched in patients (pts) presenting with mets (6/11, 55%) vs localized disease (10/59, 17%; p=0.02). The TES cohort included 23 pts with 28 profiled specimens; 14 pts (61%) presented with mets and an additional 7 (91% total) developed mets during median follow-up of 7.8 years (range 2.0-23.3). 75% of profiled specimens were mets; 9 (32%) MTAP del, 12 (43%) SCL, and 7 (25%) WT. MTAP del always co-occurred with CDKN2A del. 19 specimens were available for paired IHC. All cases with MTAP del on TES showed MTAP loss by IHC, and all SCL or WT showed retained MTAP by IHC. All pts with MTAP del by TES had MTAP loss in the primary tumor (5/7 available). Seven pts had more than one specimen available for IHC, and MTAP status was consistent across specimens with 1 intriguing exception: a patient with a primary tumor showing MTAP loss had a met with MTAP WT, both confirmed by TES and IHC.

Conclusion: MTAP del is common in GIST and enriched in pts presenting with mets. We found 100% concordance between MTAP del by TES and MTAP loss by IHC in this small series. In MTAP del cases, all available primary tumors had MTAP loss, but further studies are needed to determine if the event is truncal or subclonal. These data provide fundamental information for investigating PRMT5i in GIST with MTAP del.