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Am J Hum Genet. 2016 Jun 2;98(6):1170-1180. doi: 10.1016/j.ajhg.2016.04.014. Epub 2016 May 26.

Genomic Profiling of Thyroid Cancer Reveals a Role for Thyroglobulin in Metastasis.

Author information

1
Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
2
Department of Surgery, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
3
Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
4
Department of Diabetes and Endocrinology, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia.
5
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia. Electronic address: falkuraya@kfshrc.edu.sa.
6
Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. Electronic address: kkuraya@kfshrc.edu.sa.

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.

PMID:
27236916
PMCID:
PMC4908175
DOI:
10.1016/j.ajhg.2016.04.014
[Indexed for MEDLINE]
Free PMC Article

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