使用综合儿童癌症基因 Panel 的儿童甲状腺癌的遗传改变。
- 作者列表："Alzahrani AS","Alswailem M","Alswailem AA","Al-Hindi H","Goljan E","Alsudairy N","Abouelhoda M
CONTEXT:Pediatric differentiated thyroid cancer (DTC) differs from adult DTC in its underlying genetics and clinicopathological features. In this report, we studied these aspects in 48 cases of pediatric DTC. PATIENTS AND METHODS:We used the comprehensive Oncomine Childhood Cancer Gene panel on Ion Torrent next generation sequencing platform. We included 48 patients (37 females and 11 males) with pediatric DTC (median age 17 years, range 5-18) and studied the association between these genetic alterations and the clinicopatholgical features and outcome. RESULTS:Of 48 tumors, 33 (69%) had somatic genetic alterations which were mutually exclusive except in one tumor. BRAFV600E and RET-PTC1 were the most common occurring in 9 different tumors (19%) each. RET-PTC3 and ETV6-NTRK3 were the next most common with each of them occurring in 4 different tumors (8%). Other genetic alterations including EML4-NTRK1, EML4-ALK, NRAS, KRAS, PTEN and CREBBP occurred once each. There were no differences between those who had mutations and those without mutations in the age, sex, tumor multifocality, extrathyroidal extension, vascular invasion, lymph node or distant metastasis and the American Thyroid Association status at the last follow up visits. Similarly, none of these factors were different between those with fusion genes vs. single point mutations vs. no mutations. CONCLUSIONS:In pediatric DTC, fusion genes are more common than single point mutations. The most common genetic alterations are RET/PTC1, BRAFV600E, RET/PTC3 and ETV6-NTRK3. Other alterations occur rarely. Genetic alterations do not correlate with the clinicopathological features or the outcome.
背景: 儿童分化型甲状腺癌 (DTC) 在其潜在的遗传学和临床病理特征上与成人 DTC 不同。本文对 48 例小儿 DTC 进行了这方面的研究。 患者和方法: 我们使用了 Ion Torrent 下一代测序平台上的综合 Oncomine 儿童癌症基因 panel。我们纳入了 48 例儿童 DTC 患者 (37 例女性和 11 例男性) (中位年龄 17 岁，范围 5-18 岁)，研究了这些遗传学改变与临床病理特征和结局之间的相关性。 结果: 48 例肿瘤中，33 例 (69%) 存在体细胞遗传学改变，除 1 例肿瘤外，相互排斥。BRAFV600E 和 RET-PTC1 最常见于 9 种不同的肿瘤 (各 19%)。其次是 RET-PTC3 和 ETV6-NTRK3，分别发生在 4 种不同的肿瘤 (8%)。其他遗传改变包括 EML4-NTRK1 、 EML4-ALK 、 NRAS 、 KRAS 、 PTEN 和 CREBBP 各发生一次。有突变者与无突变者在年龄、性别、肿瘤多灶性、甲状腺外扩展、血管侵犯、淋巴结或远处转移与美国甲状腺协会末次随访状态。同样，这些因素在融合基因与单点突变与无突变之间没有差异。 结论: 在小儿 DTC 中，融合基因比单点突变更常见。最常见的遗传改变是 RET/PTC1 、 BRAFV600E 、 RET/PTC3 和 ETV6-NTRK3。其他改变很少发生。遗传改变与临床病理特征或结局无关。
METHODS:OBJECTIVES:To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS:Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS:Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS:Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.
METHODS:Background Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. Methods Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. Results In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. Conclusions The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.
METHODS::PTPN2 is one of the members of the protein Tyrosine Phosphatases (PTPs) family. To explore the promotive effect of upregulated PTPN2 induced by inflammatory response or oxidative stress on the progression of thyroid cancer. PTPN2 level in thyroid cancer tissues and cell lines was detected. Kaplan-Meier method was applied for evaluating the prognostic value of PTPN2 in thyroid cancer patients. After stimulation of inflammatory response (treatment of IFN-γ and TNF-α), or oxidative stress (treatment of H2O2), protein level of PTPN2 in K1 cells was measured by Western blot. Regulatory effects of PTPN2 on EdU-positive staining and Ki-67 positive cell ratio in K1 cells either with H2O2 stimulation or not were determined. PTPN2 was upregulated in thyroid cancer tissues and cell lines. Its level was higher in metastatic thyroid cancer patients than those of non-metastatic ones. High level of PTPN2 predicted worse prognosis of thyroid cancer. Treatment of either IFN-γ or TNF-α upregulated protein level of PTPN2 in K1 cells. Meanwhile, H2O2 stimulation upregulated PTPN2, which was reversed by NAC administration. With the stimulation of increased doses of H2O2, EdU-positive staining and Ki-67 positive cell ratio were dose-dependently elevated. Silence of PTPN2 attenuated proliferative ability and Ki-67 expression in K1 cells either with H2O2 stimulation or not. Inflammatory response or oxidative stress induces upregulation of PTPN2, thus promoting the progression of thyroid cancer.