Abstract 2001P
Background
In this study, we compared the genomic alterations (GA) in the more common salivary gland ACC (SGACC) with the less frequent tracheal (TACC) and breast (BRACC) cases.
Methods
CGP was performed on FFPE samples from clinically advanced ACC including 405 SGACC, 14 TACC and 39 BRACC. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC.
Results
TACC, BRACC and SGACC featured a similar median age and gender distribution. GA/tumor was slightly higher in TACC and BRACC. Almost all ACC were MSI stable and had low TMB. Currently untargetable GA differed with TERT, TP53 and NOTCH1 mutations higher in TACC, NOTCH, KDM6A and TERT higher in SGACC and CREBBP, TP53 and NOTCH1 higher in BRACC. Intron targeting for NFIB-MYB fusion detection was limited in this DNA sequencing only assay. MYB fusions were identified in 17% of the SGACC and 27% of BRACC, but 0% of TACC. TACC featured higher frequency of potential targets including KIT, PDFRA, and NTRK1 compared to the lower frequencies of targetable GA in SGACC and BRACC. Table: 2001P
| Trachea ACC | Salivary Gland ACC | Breast ACC | ||||
| Cases | 14 | 405 | 39 | |||
| Gender (male/female) | 57%/43% | 50%/50% | 5%/ 95% | |||
| Median Age/Range (years) | 53 (40-76) | 57 (11-89) | 62 (37-79) | |||
| GA/tumor | 3.4 | 2.9 | 3.7 | |||
| Most Frequently Altered Genes | TERT | 60% | NOTCH1 | 22% | MYB | 27% |
| NOTCH1 | 36% | MYB | 17% | CREBBP | 23% | |
| TP53 | 29% | KDM6A | 15% | TP53 | 21% | |
| KDR | 21% | TERT | 14% | NOTCH1 | 18% | |
| MYB | 0% | BCOR | 13% | KMT2D | 13% | |
| TP53 | 9% | RB1 | 10% | |||
| Potential Targetable GA | KIT | 21% | PIK3CA | 7% | EGFR | 7% |
| PDGFRA | 21% | FGFR2 | 4% | PTEN | 7% | |
| NTRK1 | 7% | PDGFRA | 3% | NF1 | 3% | |
| PIK3CA | 7% | PTEN | 3% | KIT | 3% | |
| KIT | 3% | |||||
| MSI High Status | 0% | 0.30% | 0% | |||
| TMB Median (mut/Mb) | 1.7 | 1.7 | 1.7 | |||
| TMB > 10 mut/Mb | 0% | 0.30% | 6% | |||
| PD-L1 IHC Positive | NA | 1% | 0% |
Conclusions
Although they feature similar histologies, our cohorts of TACC, SGACC and BRACC vary significantly at the molecular level. TACC featured a higher frequency of potential genomic targets including GA’s in KIT, PDFRA, and NTRK1 compared to the lower frequencies of targetable GA in SGACC and BRACC although kinase targets are uncommonly identified in these tumors as well.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine Inc.
Funding
Foundation Medicine Inc.
Disclosure
J. Elvin: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. N.A. Danziger: Full/Part-time employment: Foundation Medicine Inc.. J-A. Vergilio: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. J.K. Killian: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. D.I. Lin: Full/Part-time employment: Foundation Medicine Inc. E. Williams: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. J. Tse: Full/Part-time employment: Foundation Medicine Inc. S. Ramkissoon: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. E. Severson: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. A. Hemmerich: Full/Part-time employment: Foundation Medicine Inc. C. Edgerly: Full/Part-time employment: Foundation Medicine Inc. D. Duncan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. R. Huang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Licensing/Royalties, IHC patent: Roche/Ventana. A.B. Schrock: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. B. Alexander: Leadership role, Full/Part-time employment: Foundation Medicine Inc.; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Puma. J. Venstrom: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Full/Part-time employment: Genentech. P. Reddy: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. K. McGregor: Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc. J.S. Ross: Leadership role, Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine Inc.; Advisory/Consultancy: Celsius Therapeutics. All other authors have declared no conflicts of interest.