Genomic Profiling of Thyroid Cancer Reveals a Role for Thyroglobulin in Metastasis.
Am J Hum Genet
; 98(6): 1170-1180, 2016 06 02.
Article
em En
| MEDLINE
| ID: mdl-27236916
ABSTRACT
Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence; it is most common in Saudi Arabia, where it is only second to breast cancer as the most common cancer among females. Genomic profiling of PTC from Saudi Arabia has not been attempted previously. We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, then sequenced these genes by using a next-generation gene-panel approach in an additional 785 samples. In addition to BRAF, N-RAS, and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort. Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis. Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p < 0.001), including events of apparent clonal expansion. Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tireoglobulina
/
Neoplasias da Glândula Tireoide
/
Carcinoma Papilar
/
Genômica
/
Sequenciamento de Nucleotídeos em Larga Escala
/
Mutação
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Arábia Saudita