Abstract 1796
Background
We used CGP to compare the genomic alterations (GA) in mPara and mPheo to enable the search for potential therapy targets.
Methods
FFPE sections of 84 mPara and 44 mPheo underwent hybrid-capture based CGP. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (DAKO 22C3 antibody).
Results
All patients had recurrent and/or metastatic disease. Patient ages were similar, but mPara featured significantly more male patients (Table). The GA/tumor frequency was low for both tumor types. The most frequent un-targetable GA were in SDHB, ATRX and TERT in mPara and ATRX, TP53 and SDHB in mPheo. The most frequent potentially targetable GA in mPara were in FGFR1 (7%, primarily amplifications) and NF1, PTEN, NF2 and CDK4 (all 2%) and for mPheo were in RET (9%, primarily fusions), NF1 (9%) and FGFR1 (5%). PBRM1 GA were found in only in 1% of mPara and 2% of mPheo. Germline mutations in known cancer predisposition genes were predicted in 38 (45%) mPara and 8 (18%) mPheo cases, predominantly involving the SDHA/B genes. The TMB and PD-L1 expression levels were similar in both tumor types and 0% of cases were associated with MSI High status.Table: 512O
mPara | mPheo | |
---|---|---|
Number of Cases | 84 | 44 |
Age in years (range) | 48 (10-80) | 52 (7-78) |
Males/Females | 51/33 | 23/21 |
GA per tumor[AS1] | 1.9 | 2.3 |
Most common Untargetable GA | SDHB (27%) ATRX (21%) TERT (18%) TP53 (7%) SDHA (7%) | ATRX (25%) TP53 (21%) SDHB (13%) CTNNB1 (7%) VHL (7%) CDKN2A/2B, PIK3R2, NOTCH2 and MEN1 (all 5%) |
Most common Targetable GA | FGFR1 (7%) NF1 (2%) PTEN (2%) NF2 (2%) CDK4 (2%) | RET (9%) NF1 (9%) FGFR1 (5%) |
CD274 amplification | 0% | 0% |
PBRM1 GA | 1% | 2% |
MSI | 0% | 0% |
Median TMB mut/Mb | 1.3 | 2.4 |
TMB > 10/20 mut/Mb | 6%/2% | 5%/0% |
PD-L1 Expression low/high | 14%/0% | 0%/0% |
Conclusions
mPara and mPheo feature similar GA with mPara more often associated with germline GA. Although the GA/tumor is relatively low for mPara and mPheo, CGP can reveal important potential therapy targets in both tumor types including RET, NF1 and FGFR1. Based on biomarker assessments, mPara and mPheo do not appear to have strong potential for responsiveness to immunotherapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine.
Funding
Foundation Medicine.
Disclosure
E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J..K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. V.A. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.
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