NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States. Issue 7 (19th January 2016)

• Record Type: Journal Article
• 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.
• Is Part Of: Cancer. Volume 122:Issue 7(2016)
• Page Start: 1097
• Page End: 1107
• Publication Date: 2016-01-19
• Subjects: neurotrophic tyrosine kinase -- receptor type 3/ets variant 6 (NTRK3/ETV6) fusion oncogene -- papillary thyroid carcinoma -- pediatric cancer -- thyroid neoplasms; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29887
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2016;122:1097–1107. © 2016 American Cancer Society Abstract : Pediatric papillary thyroid carcinomas with oncogene fusions (neurotrophic tyrosine kinase receptor types 1 and 3 [ NTRK1/NTRK3 ], RET/PTC ) are associated with extensive disease and aggressive pathology. An unusually high prevalence of NTRK1/NTRK3 oncogene fusion is observed in this pediatric population from the northeast United States.