Premium
Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma
Author(s) -
Potter Samara L.,
Reuther Jacquelyn,
Chandramohan Raghu,
Gandhi Ilavarasi,
Hollingsworth Faith,
Sayeed Hadi,
Voicu Horatiu,
Kakkar Nipun,
Baksi Koel Sen,
Sarabia Stephen F.,
Lopez Monica E.,
Chelius Daniel C.,
Athanassaki Ioanna D.,
Mahajan Priya,
Venkatramani Rajkumar,
Quintanilla Norma M.,
LopezTerrada Dolores H.,
Roy Angshumoy,
Parsons D. Williams
Publication year - 2021
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28741
Subject(s) - medicine , thyroid carcinoma , fusion gene , dna sequencing , rna , cancer research , papillary thyroid cancer , gene , oncology , thyroid , biology , genetics
Background Pediatric papillary thyroid carcinoma (PTC) is clinically and biologically distinct from adult PTC. We sequenced a cohort of clinically annotated pediatric PTC cases enriched for high‐risk tumors to identify genetic alterations of relevance for diagnosis and therapy. Methods Tumor DNA and RNA were extracted from FFPE tissue and subjected to next‐generation sequencing (NGS) library preparation using a custom 124‐gene hybridization capture panel and the 75‐gene Archer Oncology Research Panel, respectively. NGS libraries were sequenced on an Illumina MiSeq. Results Thirty‐six pediatric PTC cases were analyzed. Metastases were frequently observed to cervical lymph nodes (29/36, 81%), with pulmonary metastases less commonly found (10/36, 28%). Relapsed or refractory disease occurred in 18 patients (18/36, 50%). DNA sequencing revealed targetable mutations in 8 of 31 tumors tested (26%), most commonly BRAF p.V600E ( n = 6). RNA sequencing identified targetable fusions in 13 of 25 tumors tested (52%): RET ( n = 8), NTRK3 ( n = 4), and BRAF . Mutually exclusive targetable alterations were discovered in 15 of the 20 tumors (75%) with both DNA and RNA analyzed. Fusion‐positive PTC was associated with multifocal disease, higher tumor staging, and higher American Thyroid Association risk levels. Both BRAF V600E mutations and gene fusions were correlated with the presence of cervical metastases. Conclusions Targetable alterations were identified in 75% of pediatric PTC cases with both DNA and RNA evaluated. Inclusion of RNA sequencing for detection of fusion genes is critical for evaluation of these tumors. Patients with fusion‐positive tumors were more likely to have features of high‐risk disease.