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- Title
NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States.
- Authors
Prasad, Manju L.; Vyas, Monika; Horne, Matthew J.; Virk, Renu K.; Morotti, Raffaella; Liu, Zongzhi; Tallini, Giovanni; Nikiforova, Marina N.; Christison‐Lagay, Emily R.; Udelsman, Robert; Dinauer, Catherine A.; Nikiforov, Yuri E.
- Abstract
<bold>Background: </bold>An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children.<bold>Methods: </bold>The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing.<bold>Results: </bold>Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B-Raf proto-oncogene, serine/threonine kinase (BRAF) valine-to-glutamic acid mutation at position 600 (BRAF(V) (600E)) (13 of 27 tumors; 48%), 11 measured <2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with BRAF(V) (600E) PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; P = .05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; P < .001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; P = .02); BRAF(V) (600E) PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (NTRK1/TPR, n = 1; RET/PTC1, n = 1).<bold>Conclusions: </bold>Fusion oncogene PTC presents with more extensive disease and aggressive pathology than BRAF(V) (600E) PTC in the pediatric population. The high prevalence of the NTRK1/NTRK3 fusion oncogene PTCs in the United States is unusual and needs further investigation.
- Subjects
THYROID cancer; HISTOPATHOLOGY; ONCOGENES; PROTEIN-tyrosine kinases; METASTASIS
- Publication
Cancer (0008543X), 2016, Vol 122, Issue 7, p1097
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.29887