Pediatric, adolescent, and young adult thyroid carcinoma harbors frequent and diverse targetable genomic alterations, including kinase fusions

Pierre Vanden Borre, Alexa B. Schrock, Peter M. Anderson, John C. Morris, Andreas M. Heilmann, Oliver Holmes, Kai Wang, Adrienne Johnson, Steven G. Waguespack, Sai Hong Ignatius Ou, Saad Khan, Kar Ming Fung, Philip J. Stephens, Rachel L. Erlich, Vincent A. Miller, Jeffrey S. Ross, Siraj M. Ali

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)255-263
Number of pages9
JournalOncologist
Volume22
Issue number3
DOIs
StatePublished - Mar 2017

Keywords

  • Comprehensive genomic profiling
  • Fusion
  • Genomics
  • Molecular targeted therapy
  • Oncogene proteins
  • Thyroid carcinoma
  • Vandetanib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Borre, P. V., Schrock, A. B., Anderson, P. M., Morris, J. C., Heilmann, A. M., Holmes, O., Wang, K., Johnson, A., Waguespack, S. G., Ou, S. H. I., Khan, S., Fung, K. M., Stephens, P. J., Erlich, R. L., Miller, V. A., Ross, J. S., & Ali, S. M. (2017). Pediatric, adolescent, and young adult thyroid carcinoma harbors frequent and diverse targetable genomic alterations, including kinase fusions. Oncologist, 22(3), 255-263. https://doi.org/10.1634/theoncologist.2016-0279