Application of genomics to identify therapeutic targets in recurrent pediatric papillary thyroid carcinoma
- Rebecca Ronsley1,
- S. Rod Rassekh2,3,
- Yaoqing Shen4,
- Anna F. Lee5,
- Colleen Jantzen3,
- Jessica Halparin3,
- Catherine Albert6,
- Douglas S. Hawkins6,
- Shazhan Amed1,
- Ralph Rothstein1,
- Andrew J. Mungall4,
- David Dix3,
- Geoffrey Blair7,
- Helen Nadel8,
- Steven J.M. Jones4,
- Janessa Laskin9,11,
- Marco A. Marra4,10,11 and
- Rebecca J. Deyell2,3,11
- 1Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
- 2BC Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada;
- 3Division of Oncology and Hematology, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
- 4Canada's Michael Smith Genome Science Centre, British Columbia Cancer, Vancouver, British Columbia V5Z 4S6, Canada;
- 5Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
- 6Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington 98105, USA;
- 7Department of Surgery, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
- 8Department of Radiology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
- 9British Columbia Cancer, Vancouver, British Columbia V5Z 4S6, Canada;
- 10Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
- Corresponding author: rdeyell{at}cw.bc.ca
-
↵11 Co-senior authors
Abstract
Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A TPM3-NTRK1 fusion was identified in one tumor, with outlier NTRK1 expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A RET fusion was identified in the second tumor, another potentially actionable finding. Identification of oncogenic drivers in recurrent pediatric PTC may facilitate targeted therapy while avoiding repeated RAI.
- Received December 15, 2017.
- Accepted February 3, 2018.
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