Genetic landscape of papillary thyroid carcinoma in the Chinese population

Abstract

Improvement in the clinical outcome of human cancers requires characterization of the genetic alterations underlying their pathogenesis. Large-scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease, while, so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a large-scale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer. By performing targeted DNA amplicon and targeted RNA deep-sequencing, we elucidated the landscape of somatic genetic alterations in 355 Chinese patients with PTC. A total of 88.7% of PTCs were found to harbor at least one candidate oncogenic driver genetic alteration. Among them, around 72.4% of the cases carried BRAF mutations; 2.8% of cases harbored RAS mutations; and 13.8% of cases were characterized with in-frame gene fusions, including seven newly identified kinase gene fusions. TERT promoter mutations were likely to occur in a sub-clonal manner in our PTC cohort. The prevalence of somatic genetic alterations in PTC was significantly different between our Chinese cohort and TCGA datasets for American patients. Additionally, combined analyses of genetic alterations and clinicopathologic features demonstrated that kinase gene fusion was associated with younger age at diagnosis, larger tumor size, and lymph node metastasis in PTC. With the analyses of DNA rearrangement sites of RET gene fusions in PTC, signatures of chromosome translocations related to RET fusion events were also depicted. Collectively, our results provide fundamental insight into the pathogenesis of PTC in the Chinese population. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley& Sons, Ltd.

Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis

“…It has been reported that BRAF mutation is more common in Asian populations ( eg Korean), which may be associated with higher iodine intake in Asian populations 25 . Our result was consistent with another Chinese study in which BRAF mutation accounted for 72.4% of cases 12 . In contrast, RAS family mutation seems to be higher in Europe and America.…”

“…According to the guidelines of the American Thyroid Association, DM‐PTC were considered at high risk and usually require more aggressive treatments ( eg total thyroidectomy, extensive lymph node dissection, intensive radioactive iodine (RAI) therapy and intense TSH suppression therapy) 4 . Several studies have investigated the genetic characteristics of PTC from genome and transcriptome levels in various geographic regions or ethnicity background 11‐14 . However, due to the low incidence of distant metastasis in PTC, there are few studies on the genetic landscape of DM‐PTC.…”

Targeted next‑generation sequencing of cancer‑related genes in thyroid carcinoma: A single institution's experience

“…However, the higher frequency could also be attributed to tumors in patients from specific geographic locations and to methodologic differences. Recent studies from eastern Asia demonstrated a higher frequency of approximately 80% for the BRAF V600E mutation in PC, which is consistent with our results (24)(25)(26)(27). Residents in eastern Asia commonly consume seaweeds as a part of their regular diet.…”

Columnar Cell Variant of Papillary Thyroid Carcinoma: A Clinicopathologic Analystis

“…The prognosis of papillary thyroid carcinoma is good. 10year survival rate more is than 90%, especially in young patients (98%) [12][13][14][15][16][17]. The factors affecting the prognosis included vascular invasion, nuclear atypia, tumor size and age.…”