We queried whether CGP could differentiate the mTC subtypes of papillary (PTC), follicular (FTC), medullary (MTC) and anaplastic (ATC) carcinomas and their potential responses to targeted and immunotherapies.
CGP was performed on FFPE samples using hybridization-captured, adaptor ligation based libraries to a mean coverage depth of > 500X for up to 315 cancer-related genes. Total mutational burden (TMB) was determined on 1.1 megabases of sequenced DNA as previously described (PMID: 28420421).
778 clinically advanced mTC were studied. Median age across the subtypes was similar with male patients slightly more frequent than females except for PTC. ATC had the highest median GA/sample at 4.34. BRAF was a target option for 73% of PTC and 39% of ATC, and RET for MTC in 81% of cases. Oncogenic rearrangements of RET, BRAF, ALK, and NTRK1 were detected in 8%, 3%, 1%, and 1% of PTC cases, respectively, and in 1%, 1%, 0%, and 1% of ATC cases, respectively, but not detected in any cases of FTC or MTC. At 66%, TP53 GA were most frequent in ATC. TERT GA were 58-67% in PTC, FTC and ATC and 0% in MTC. TMB was extremely low for all 4 mTC tumor types with only 3 mTC (
Refractory mTC patients are generally older than patients with classic localized primary PTC, and feature relatively more males. Advanced stage PTC, and to a lesser extent ATC, is frequently driven by BRAF GA or oncogenic rearrangements. Relapsed MTC is nearly universally driven by RET GA, whereas FTC has no dominant driver GA identified. TMB appears to be low for all subtypes of MTC, suggesting low potential for immunotherapies.
Clinical trial identification
Legal entity responsible for the study
Jeffrey S. Ross
J.S. Ross: Employee, leader and stock owner in Foundation Medicine. L.M. Gay, P. Vanden Borre, N. Almog, A.B. Schrock, J-A. Vergilio, J. Suh, S. Ramkissoon, E. Severson, S. Daniel, S.M. Ali, J.A. Elvin: Employee and stock owner in Foundation Medicine. V.A. Miller, P.J. Stephens: Employee, leader stock ower in Foundation Medicine. All other authors have declared no conflicts of interest.