ESPE Abstracts (2019) 92 FC5.3

ESPE2019 Free Communications Thyroid (6 abstracts)

Predominant DICER1 Mutations in Pediatric Follicular Thyroid Carcinomas

Young Ah Lee 1 , Sun-Wha Im 2 , Kyeong Cheon Jung 3 , Eun Jae Chung 4 , Choong Ho Shin 1 , Jong-II Kim 2,5,6 & Young Joo Park 7

1Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea, Republic of. 2Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea, Republic of. 3Department of Pathology, Seoul National University College of Medicine, Seoul, Korea, Republic of. 4Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea, Republic of. 5Department of Biomedical Sciences, Seoul National University Graduate School,, Seoul, Korea, Republic of. 6Seoul National University Cancer Research Institute, Seoul, Korea, Republic of. 7Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea, Republic of

Background: Pediatric thyroid cancer has characteristics that are distinct from adulthood thyroid cancer. Due to its very low prevalence, little is known about the genetic characteristics of pediatric follicular thyroid cancer (FTC).

Methods: We investigated genetic alterations in tumor tissues from 15 patients aged < 20 years (median: 14.3 years; range: 2.4-19.0 years) using multifaceted approaches. Whole-exome sequencing, targeted next-generation sequencing using a cancer gene panel, and Sanger sequencing of the major exons of the H/K/N-RAS and DICER1 genes and the promoter region of the TERT gene, were performed. Normal tissues and blood of patients with DICER1-positive tumors were also evaluated to determine the germline DICER1 mutation.

Results: The median tumor size was 3.1 cm (range: 0.6-6.4 cm). Four patients exhibited angioinvasion, and one extensive capsular invasion; none showed evidence of disease over a median of 7.6 years. Eight patients (53.3%) had DICER1 mutations, including four with DICER1 syndrome (three patients were <10 years of age). A PTEN frameshift mutation (n = 1), PAX8/PPARγ rearrangement (n = 1), and multiple loss of heterozygosity with or without copy number alterations (n = 2) were detected. No RAS or TERT mutations were found. Nodular hyperplasia and follicular adenoma (FA) coexisted in DICER1 mutation-positive FTCs more frequently than mutation-negative FTCs (P=0.026). All DICER1 mutation-positive FTCs had a somatic missense mutation at metal binding sites (six at codon E1813 and two at codon D1709) within the RNase IIIb domain; seven had other missense, nonsense, or frameshift mutations in the DICER1 gene. Six coexisting FAs of two patients with DICER1 syndrome (three of each) had additional somatic mutations at metal binding sites within the RNase IIIb domain (codon E1705, D1709, D1810 or E1813), different from each other and from the indexed FTC tumor.

Conclusions: Pediatric FTCs had distinct genomic alterations and pathogenesis compared to adults, particularly those characterized by DICER1 mutations. The DICER1 mutation should be considered in pediatric FTCs, especially in cases < 10 years of age. In all DICER1-mutated FTCs and FAs, recurrent hotspot mutations were found at metal binding sites within the RNase IIIb domain, suggesting their impact on tumorigenesis.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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