TY - JOUR
T1 - Pediatric, adolescent, and young adult thyroid carcinoma harbors frequent and diverse targetable genomic alterations, including kinase fusions
AU - Borre, Pierre Vanden
AU - Schrock, Alexa B.
AU - Anderson, Peter
AU - Morris, John C.
AU - Heilmann, Andreas M.
AU - Holmes, Oliver
AU - Wang, Kai
AU - Johnson, Adrienne
AU - Waguespack, Steven G.
AU - Ou, Sai Hong Ignatius
AU - Khan, Saad
AU - Fung, Kar Ming
AU - Stephens, Philip J.
AU - Erlich, Rachel L.
AU - Miller, Vincent A.
AU - Ross, Jeffrey S.
AU - Ali, Siraj M.
N1 - Publisher Copyright:
© AlphaMed Press 2017.
PY - 2017/3
Y1 - 2017/3
N2 - Background. Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity andmortality. Methods. Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety-three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of theseMTC patients with novel alterations in RETexperienced clinical benefit fromvandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy.
AB - Background. Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity andmortality. Methods. Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety-three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of theseMTC patients with novel alterations in RETexperienced clinical benefit fromvandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy.
KW - Comprehensive genomic profiling
KW - Fusion
KW - Genomics
KW - Molecular targeted therapy
KW - Oncogene proteins
KW - Thyroid carcinoma
KW - Vandetanib
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U2 - 10.1634/theoncologist.2016-0279
DO - 10.1634/theoncologist.2016-0279
M3 - Article
C2 - 28209747
AN - SCOPUS:85015191840
SN - 1083-7159
VL - 22
SP - 255
EP - 263
JO - Oncologist
JF - Oncologist
IS - 3
ER -