DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma

Wasserman, Jonathan D.; Sabbaghian, Nelly; Fahiminiya, Somayyeh; Chami, Rose; Mete, Özgür; Acker, Meryl; Wu, Mona; Shlien, Adam; Kock, Leanne de; Foulkes, William D.

doi:10.1210/jc.2017-02698

Cited by 97 publications

(91 citation statements)

References 25 publications

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“…On the other hand, some of the most common genetic alterations of adult PTC are rare or absent in pediatric PTC, supporting the hypothesis that biological features of PTC may differ by patient age . For instance, BRAF V600E mutation represents the most prevalent event in PTC reported in adults (23–63%) but the prevalence is lower (3–48%) in pediatric PTC patients in most studies . BRAF fusion has rarely been reported in adult PTC, whereas it has been described in radiation‐exposed pediatric PTC .…”

Section: Introductionmentioning

confidence: 61%

“…12,14,[22][23][24][25][26] For instance, BRAF V600E mutation represents the most prevalent event in PTC reported in adults (23-63%) but the prevalence is lower (3-48%) in pediatric PTC patients in most studies. 12,14,[27][28][29][30][31][32][33][34][35] BRAF fusion has rarely been reported in adult PTC, whereas it has been described in radiation-exposed pediatric PTC. 13,[36][37][38] The most prevalent BRAF fusions reported in radiation-exposed pediatric PTC are AKAP9-BRAF and AGK-BRAF.…”

Section: Introductionmentioning

confidence: 99%

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AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

Sisdelli

Cordioli

Vaisman

et al. 2019

Pediatric Blood & Cancer

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Background The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen‐activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation‐exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. Procedure In this study, we investigated the prevalence of BRAF alterations (AGK‐BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK‐BRAF fusion was investigated by RT‐PCR and confirmed by FISH break‐apart. The BRAF V600E mutation was screened using Sanger sequencing. Results AGK‐BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. Conclusion Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

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Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

Sisdelli

Cordioli

Vaisman

et al. 2019

Pediatric Blood & Cancer

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“…The outcome of the inaugural International DICER1 Symposium was the development of consensus testing and surveillance as well as treatment recommendations. Recommendations for genetic testing—including intronic sequencing [ 103 ]; whole exome sequencing [ 104 ]; or screening products such as the ThyroSeq, which is a DNA- and RNA-based next-generation sequencing assay that analyzes 112 genes for genetic alterations, including point mutations, insertions/deletions, gene fusions, and copy number alterations [ 105 ], prenatal management—and surveillance for DICER1-associated symptoms have been developed and described in recent publications [ 106 , 107 , 108 ].…”

Section: Discussionmentioning

confidence: 99%

DICER1 Syndrome: DICER1 Mutations in Rare Cancers

Robertson

Jorcyk

Oxford

2018

Cancers

133

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DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions for future research are discussed.

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“…However, in the TCGA data, we did not observe any pathogenic variation in DICER1 in the germline sequence for thyroid carcinoma; we did observe a LP (nonhotspot missense) variant in one participant with a thyroid carcinoma. One previous report found two TCGA thyroid cancers that harbored DICER1 somatic hotspot variation (Wasserman et al, 2018). The lack of observed germline pathogenic DICER1 variation in TCGA thyroid carcinomas may be secondary to study tissue requirements, which mandated sufficient tumor size with at least 60% tumor nuclei (https://cancergenome.nih.gov/cancersselected/biospeccriteria); this may have biased the study to more severe or aggressive tumors.…”

Section: Discussionmentioning

confidence: 99%

The prevalence of germline DICER1 pathogenic variation in cancer populations

Kim

Schultz

Hill

et al. 2019

Molec Gen & Gen Med

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Background The DICER1 syndrome is an autosomal dominant tumor‐predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense variation in “hotspot” codons in the RNaseIIIb domain (E1705, D1709, G1809, D1810, E1813) is observed in DICER1 ‐associated tumors. Previously, we found the prevalence of germline pathogenic DICER1 variation in the general population is 1:10,600. In this study, we investigated the prevalence of pathogenic DICER1 germline variation in The Cancer Genome Atlas (TCGA; 32 adult cancer types; 9,173 exomes) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET; two pediatric cancer types; 175 exomes) cohorts. Methods All datasets were annotated and binned into four categories: pathogenic, likely pathogenic, variant of unknown significance, or likely benign. Results The prevalence of DICER1 pathogenic variants was 1:4,600 in TCGA. A single participant with a uterine corpus endometrial carcinoma harbored two pathogenic germline DICER1 (hotspot and splice‐donor) variants, and a single participant with a rectal adenocarcinoma harbored a germline DICER1 stop‐gained variant. In the smaller TARGET dataset, we observed no pathogenic germline variants. Conclusion This is the largest comprehensive analysis of DICER1 pathogenic variation in adult and pediatric cancer populations using publicly available data. The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.

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DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma

Cited by 97 publications

References 25 publications

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

DICER1 Syndrome: DICER1 Mutations in Rare Cancers

The prevalence of germline DICER1 pathogenic variation in cancer populations

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