甲状腺癌相关基因研究进展

Advances in studies of the genes related to thyroid carcinoma

甲状腺癌（thyroid carcinoma,TC）是最常见的内分泌系统恶性肿瘤之一,其发病率逐年上升.随着甲状腺癌研究在基因水平上的不断深入,已发现多种基因与甲状腺癌的发生、发展以及预后相关,为甲状腺癌的早期诊断,预后判断和靶向治疗都提供了全新的方向.BRAF基因是甲状腺乳头状癌（papillary thyroid carcinoma,PTC）的特异性基因,不仅可以作为预后的评估标志物,还具有诊断价值.RET基因存在两种变异形式：PTC与RET基因融合关系最为密切,其分布与多种因素有关,虽然尚无文献证实术前细胞针吸活检测定RET基因重排可有效改善手术策略,但抑制RET蛋白酶活性的相关药物也许可以用来治疗PTC;而RET基因突变对甲状腺髓样癌（medullary thyroid cancer,MTC）尤其对家族性甲状腺髓样癌（familial medullar thyroid carcinoma,FMTC）的筛查和诊断有特定的意义.RAS基因突变常出现在甲状腺滤泡癌（follicular thyroid carcinoma,FTC）、甲状腺乳头状癌滤泡亚型（follicular variant of papillary thyroid carcinoma,FvPTC）、低分化甲状腺癌（poorly differentiated thyroid carcinoma,PDTC）以及未分化甲状腺癌（undifferentiated thyroid carcinoma,UTC） 中,但RAS基因突变与预后的关系尚不清楚.P53蛋白异常或TP53基因突变见于各种侵袭性较强的甲状腺乳头状癌亚种、PDTC以及UTC.TP53基因突变或P53蛋白异常不仅可用于判断预后,还为新药物的研发提供了靶点.30％～ 35％ FTC以及37.5％ FvPTC可检出PAX8-PPARγ融合基因,有助于甲状腺腺瘤的鉴别诊断.近年来发现吡格列酮可能对PAX8-PPARγ融合基因阳性的患者具有一定疗效.TERT启动子突变可在FTC以及部分PTC中检出,常提示预后不良.其他多种基因均发现与甲状腺癌相关,并可用于诊断以及提示预后.

Thyroid carcinoma （TC） is the most common endocrine cancer and its incidence has been increasing globally over the past decades.With the development of the genetic technology,more and more evidences showed that many genes affect the biological behaviors of TC,making sense to early diagnosis,predicting the prognosis and targeted therapy for TC.BRAF mutation is specific to papillary thyroid carcinoma （PTC）.It can not only predict the prognosis,but also have diagnosis value.RET rearrangements are identified as a specific genetic event in PTC.Though the preoperative detection of RET/ PTC rearrangements has not proven useful in choosing the appropriate surgical management,new medications which are capable of inhibiting RET protein kinase activity may help to therapy the PTCs.RET mutation has specific meaning for detecting familial medullar thyroid carcinoma.Though RAS mutation can be discovered in follicular thyroid carcinoma （FTC）,follicular variant of papillary thyroid carcinoma （FvPTC）,poorly differentiated thyroid carcinoma （PDTC） and undifferentiated thyroid carcinoma （UTC）,the relationship between RAS mutation and prognosis remains controversial.P53 can be detected in more invasive variants of PTC,PDTC and UTC.P53 can be used as a prognosis-predictor.Rescuing the function of mutant p53 （mutp53） protein is an attractive anticancer therapeutic strategy.30%-35% FTC and 37.5% FvPTC have PAX8-PPAR-γ rearrangement,which can distinguish carcinomas from adenomas in follicular neoplasms of the thyroid.Pioglitazone may have therapeutic efficacy in patients with PPFP-positive TCs.FTC and PTC have TERT promoter mutation,usually predicting poor prognosis.Other genes also influence on the biological behavior of TC,having diagnosis value and prognostic significance.Though the gene study about TC develops rapidly,many problems remain unclear.Further studies on TC-related genes are needed.