二代测序技术检测甲状腺乳头状癌RET基因融合及其临床病理特征

Detection of RET Gene Fusion in Papillary Thyroid Carcinoma by Next-Generation Sequencing and its Clinicopathological Features

目的探讨甲状腺乳头状癌(PTC)患者RET基因融合及其临床病理特征。方法通过二代测序(NGS)技术对442例PTC患者进行基因检测;同时收集患者资料,探讨RET融合与临床病理特征的关系。结果(1)442例中,RET融合24例,其中RET-CCDC6融合16例,RET-NCOA4融合6例,RET-ERC1融合2例。(2)RET融合患者24例中,男性4例,女性20例;年龄9~75岁;肿瘤最大径0.2~3.6 cm;单灶11例,多灶13例;单侧16例,双侧8例;侵犯被膜5例,未侵犯被膜19例;甲状腺外侵犯10例,无腺外侵犯14例;淋巴结转移20例,无淋巴结转移4例。(3)RET融合与肿瘤最大径(P<0.001)、肿瘤单/双侧(P=0.020)、淋巴结转移(P=0.005)相关,与年龄、性别、癌灶分布、侵犯被膜、腺外侵犯、组织学亚型无关。(4)不同突变丰度的RET融合与肿瘤最大径(P<0.001)、肿瘤单/双侧(P=0.049)、淋巴结转移(P=0.018)相关,与其他临床病理特征无关。(5)RET-CCDC6融合仅与肿瘤最大径(P=0.001)相关,RET-NCOA4融合仅与肿瘤单/双侧(P=0.005)相关。结论RET基因融合与PTC患者多项不良预后因素相关,通过NGS检测RET基因融合能够辅助临床分层管理。

Objective It is to investigate the fusion of RET gene and its clinicopathological characteristics in patients with thyroid papillary carcinoma(PTC).Methods Genetic testing was performed in 442 PTC patients by next-generation sequencing(NGS)technology;patient data were also collected to explore the relationship between RET fusion and clinicopathological features.Results(1)In 442 PTC patients,24 cases of RET fusion were detected,including 16 cases of RET-CCDC6 fusion,6 cases of RET-NCOA4 fusion,and 2 cases of RET-ERC1 fusion.(2)There were 4 males and 20 females in RET fusion patients with age ranging from 9 to 75 years.The maximum diameter of tumor ranged from 0.2 to 3.6 cm.The tumors were unifocal in 11 patients and multifocal in 13 patients;unilateral in 16 patients and bilateral in 8 patients;tumor invasion of the tegument in 5 patients and no invasion of the tegument in 19 patients;extrathyroidal invasion in 10 patients and no extraglandular invasion in 14 patients;lymph node metastasis in 20 patients and no lymph node metastasis in 4 patients.(3)RET fusion was associated with tumor maximum diameter(P<0.001),unilateral/bilateral tumor(P=0.020),and lymph node metastasis(P=0.005),independent of age,gender,tumor focus distribution,invasion of perineurium,extra-glandular invasion,and histological subtypes.(4)RET fusion with different mutation abundance was associated with maximum tumor diameter(P<0.001),unilateral/bilateral tumor(P=0.049),and lymph node metastasis(P=0.018)of PTC patients,independent of other clinicopathological features.(5)RET-CCDC6 fusion was only related to the maximum tumor diameter(P=0.001)in PTC patients,and RET-NCOA4 fusion was only related to tumor unilateral/bilateral(P=0.005).Conclusion RET gene fusion is associated with many adverse prognostic factors in PTC patients.Detection of RET gene fusion by NGS can assist in clinical stratification management.