Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma

Potter, Samara L; Reuther, Jacquelyn; Chandramohan, Raghu; Gandhi, Ilavarasi; Hollingsworth, Faith; Sayeed, Hadi; Voicu, Horatiu; Kakkar, Nipun; Baksi, Koel Sen; Sarabia, Stephen F.; López, Mónica E.; Chelius, Daniel C.; Athanassaki, Ioanna; Mahajan, Priya; Venkatramani, Rajkumar; Quintanilla, Norma; López‐Terrada, Dolores; Roy, Angshumoy; Parsons, D. Williams

doi:10.1002/pbc.28741

Cited by 18 publications

(15 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The limited genomic data in this cohort support this theory. Potter et al recently published an analysis of alteration of DNA and RNA sequences in children and young adults with DTC and distant metastases, from which a higher proportion of fusion mutations were found in those with larger primary tumors (T2 and higher) (6). This raises the possibility that primary tumor size may be a proxy for the underlying genotype and supports the findings of the present study.…”

Section: Cancer Is Evolvingsupporting

confidence: 89%

Understanding of Pulmonary Metastases in Pediatric Patients with Differentiated Thyroid Cancer Is Evolving

Meister

Orloff

2021

Clinical Thyroidology

View full text Add to dashboard Cite

BackgroundLung metastases present more commonly and with better survival rates in children and young adults than in older adults with differentiated thyroid cancer (DTC). However, given the fairly low incidence of pediatric thyroid cancer, there is a paucity of literature about the clinical considerations among children and young adults with lung metastases. This retrospective study was performed to illustrate clinical considerations of lung metastases among children and young adults including associated factors, clinical presentation, and responses to therapy (1).

show abstract

Section: Cancer Is Evolvingsupporting

confidence: 89%

Understanding of Pulmonary Metastases in Pediatric Patients with Differentiated Thyroid Cancer Is Evolving

Meister

Orloff

2021

Clinical Thyroidology

View full text Add to dashboard Cite

show abstract

“…In the reports from other countries, a 9.0% (12/133) prevalence was found cumulatively in four studies of sporadic PTCs from the U.S. [29,[32][33][34]]. An 8.6% (3/35) prevalence was reported in a Brazilian study [35], and an 11.1% (1/9) in childhood PTC from Japan [36].…”

Section: Etv6/ntrk3mentioning

confidence: 92%

Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus

Rogounovitch

Mankovskaya

Fridman

et al. 2021

Cancers

View full text Add to dashboard Cite

Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) BRAFV600E, 4 (11.8%) RET/PTC1, 6 (17.6%) RET/PTC3, 2 (5.9%) rare fusion genes, and 6 (17.6%) ETV6ex4/NTRK3. No mutations in codons 12, 13, and 61 of K-, N- and H-RAS, BRAFK601E, or ETV6ex5/NTRK3 or AKAP9/BRAF were detected. Fusion genes were significantly more frequent than BRAFV600E (p = 0.002). Clinicopathologically, RET/PTC3 was associated with solid growth pattern and higher tumor aggressiveness, BRAFV600E and RET/PTC1 with classic papillary morphology and mild clinical phenotype, and ETV6ex4/NTRK3 with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type.

show abstract

“…[12][13][14] RAS mutations and PAX8-PPARG fusions were more commonly associated with fvPTC and FTCs than the other genotypes. There were four NRAS p.Q61R and one PAX8-PPARG fusion in five encapsulated fvPTC, one NRAS p.Q61R in a cPTC, one PAX8/PPARG in a cPTC/ fvPTC/svPTC mixed histology, and a single HRAS p.Q61R and single KRAS p.G12V in two FTC samples.…”

mentioning

confidence: 99%

Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers

Franco

Ricarte-Filho

Isaza

et al. 2022

JCO

View full text Add to dashboard Cite

PURPOSE In 2014, data from a comprehensive multiplatform analysis of 496 adult papillary thyroid cancer samples reported by The Cancer Genome Atlas project suggested that reclassification of thyroid cancer into molecular subtypes, RAS-like and BRAF-like, better reflects clinical behavior than sole reliance on pathologic classification. The aim of this study was to categorize the common oncogenic variants in pediatric differentiated thyroid cancer (DTC) and investigate whether mutation subtype classification correlated with the risk of metastasis and response to initial therapy in pediatric DTC. METHODS Somatic cancer gene panel analysis was completed on DTC from 131 pediatric patients. DTC were categorized into RAS-mutant ( H-K-NRAS), BRAF-mutant ( BRAF p.V600E), and RET/ NTRK fusion ( RET, NTRK1, and NTRK3 fusions) to determine differences between subtype classification in regard to pathologic data (American Joint Committee on Cancer TNM) as well as response to therapy 1 year after initial treatment had been completed. RESULTS Mutation-based subtype categories were significant in most variables, including age at diagnosis, metastatic behavior, and the likelihood of remission at 1 year. Patients with RET/ NTRK fusions were significantly more likely to have advanced lymph node and distant metastasis and less likely to achieve remission at 1 year than patients within RAS- or BRAF-mut subgroups. CONCLUSION Our data support that genetic subtyping of pediatric DTC more accurately reflects clinical behavior than sole reliance on pathologic classification with patients with RET/ NTRK fusions having worse outcomes than those with BRAF-mutant disease. Future trials should consider inclusion of molecular subtype into risk stratification.

show abstract

Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma

Cited by 18 publications

References 45 publications

Understanding of Pulmonary Metastases in Pediatric Patients with Differentiated Thyroid Cancer Is Evolving

Understanding of Pulmonary Metastases in Pediatric Patients with Differentiated Thyroid Cancer Is Evolving

Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus

Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers

Contact Info

Product

Resources

About