Mutational analysis using next generation sequencing in pediatric thyroid cancer reveals BRAF and fusion oncogenes are common. (June 2022)

• Record Type: Journal Article
• Authors: Newfield, Ron S.; Jiang, Wen; Sugganth, Daniel X.; Hantash, Feras M.; Lee, Euyhyun; Newbury, Robert O.
• Is Part Of: International journal of pediatric otorhinolaryngology. Volume 157(2022)
• Publication Date: 2022-06
• Subjects: NGS -- Pediatric -- Well-differentiated thyroid carcinoma -- Fusion-oncogenes -- BRAF -- RET-PTC; NGS Next Generation Sequencing; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Otolaryngology -- Periodicals; Pediatrics -- Periodicals; Oto-rhino-laryngologie -- Périodiques; Pédiatrie -- Périodiques; 618.9209751
• DOI: 10.1016/j.ijporl.2022.111121
• Languages: English
• ISSNs: 0165-5876

Abstract

Abstract: Background: We previously described mutation rates of BRAF V600E, RAS, RET-PTC and PAX8-PPARγ in pediatric subjects with well-differentiated thyroid cancer (WDTC). We expanded the cohort adding next-generation sequencing (NGS) and assessed genotype-phenotype correlations. Methods: Single-center retrospective cohort examining thyroidectomy tissue blocks from consecutive pediatric WDTC patients between 2001 and 2015. Tissues were analyzed at Quest Diagnostics for BRAF, RAS mutations, RET-PTC and PAX8-PPARγ, and additional fusions, using standalone and NGS tests. WDTC included papillary (PTC), follicular (FTC) and follicular-variant PTC (FVPTC). Results: We genotyped 46 samples (36 females). Mean age at diagnosis was 14.7 years and the cohort comprised of mostly Hispanic (60.9%) and Caucasian (26.1%) patients. Mean follow-up was 3.5 years. Genetic alterations (GA) were noted in 69.6%, with BRAF V600E (n = 11), and RET-PTC (n = 8) detected only in PTC. GA were detected in 2/7 FTC (1 PAX8-PPARγ, 1 NRAS ) and 6/10 FVPTC (3 PAX8-PPARγ, 1 STRN-ALK, 1 BRAF K601E, 1 NRAS ). Patients with BRAF V600E were predominantly Hispanic (81.8%) and >15 years (81.8%), whereas 87.5% RET-PTC and 50% other-fusions occurred in patients ≤15 years (p = 0.044). Of the 29 PTC patients, 82.8% had GA: BRAF V600E (37.9%), RET-PTC (27.6%), 17.2% other fusion-oncogenes (2 - ALK, 3 - NTRK ). Non- RET fusions had the highest vascular invasion (100%, p = 0.042 vs RET-PTC ) and frequent lymphatic invasion (80%). GA were most common in PTC with cervical metastasis. Conclusions: BRAF V600E was the most common single mutation, especially in older and Hispanic adolescents. All fusions combined are more common than BRAF V600E . NGS reveals a genetic basis in most pediatric WDTC, which may have implications for the role of molecular testing and systemic therapy. Highlights: Fusions are common in pediatric PTC. Fusions with more invasion ≠ more metastases. BRAF V600E was the most common single-gene mutation. About half of PTC patients had Hashimoto's thyroiditis.