透明细胞肾细胞癌的放射组基因组学：CT 成像特征与突变之间的关联。
Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging features and mutations.
机构信息
From the Genitourinary Imaging Group, Department of Radiology (C.A.K., P.L.D.P., J.C., H.H., O.A.), Urology Service, Department of Surgery (A.A.H., P.R.), Human Oncology & Pathogenesis Program (A.A.H., J.J.H.), Department of Epidemiology and Biostatistics (I.O.), and Department of Medicine, Genitourinary Oncology Service (R.M., J.J.H.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Radiology Academic Offices, Room C278, New York, NY 10065.
出版信息
Radiology. 2014 Feb;270(2):464-71. doi: 10.1148/radiol.13130663. Epub 2013 Oct 28.
PURPOSE
To investigate associations between computed tomographic (CT) features of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2, KDM5C, or BAP1 genes.
MATERIALS AND METHODS
The institutional review board approved this retrospective, hypothesis-generating study of 233 patients with clear cell RCC and waived the informed consent requirement. The study was HIPAA compliant. Three radiologists independently reviewed pretreatment CT images of all clear cell RCCs without knowledge of their genomic profile. One radiologist measured largest diameter and enhancement parameters of each clear cell RCC. Associations between CT features and mutations in VHL, PBRM1, SETD2, KDM5C, and BAP1 genes were tested by using the Fisher exact test. Associations between mutations and size and enhancement were assessed by using the independent t test. Interreader agreement was calculated by using the Fleiss κ.
RESULTS
Mutation frequencies among clear cell RCCs were as follows: VHL, 53.2% (124 of 233); PBRM1, 28.8% (67 of 233); SETD2, 7.3% (17 of 233); KDM5C, 6.9% (16 of 233); and BAP1, 6.0% (14 of 233). Mutations of VHL were significantly associated with well-defined tumor margins (P = .013), nodular tumor enhancement (P = .021), and gross appearance of intratumoral vascularity (P = .018). Mutations of KDM5C and BAP1 were significantly associated with evidence of renal vein invasion (P = .022 and .046, respectively). The genotype of solid clear cell RCC differed significantly from the genotype of multicystic clear cell RCC. While mutations of SETD2, KDM5C, and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly more common among solid clear cell RCC. Interreader agreement for CT feature assessments ranged from substantial to excellent (κ = 0.791-0.912).
CONCLUSION
This preliminary radiogenomics analysis of clear cell RCC revealed associations between CT features and underlying mutations that warrant further investigation and validation.
目的
研究透明细胞肾细胞癌（RCC）的计算机断层扫描（CT）特征与 VHL、PBRM1、SETD2、KDM5C 或 BAP1 基因突变之间的关系。
材料与方法
本研究回顾性地分析了 233 例透明细胞 RCC 患者，该研究得到了机构审查委员会的批准，并豁免了知情同意的要求，研究符合 HIPAA 规定。3 位放射科医生独立对所有透明细胞 RCC 的 CT 图像进行了评估，且不了解他们的基因组图谱。一位放射科医生测量了每个透明细胞 RCC 的最大直径和增强参数。采用 Fisher 精确检验来检验 CT 特征与 VHL、PBRM1、SETD2、KDM5C 和 BAP1 基因突变之间的关系。采用独立 t 检验评估突变与大小和增强之间的关系。采用 Fleiss κ 计算观察者间的一致性。
结果
透明细胞 RCC 的突变频率如下：VHL，53.2%（124/233）；PBRM1，28.8%（67/233）；SETD2，7.3%（17/233）；KDM5C，6.9%（16/233）；BAP1，6.0%（14/233）。VHL 的突变与边界清晰的肿瘤（P =.013）、结节样肿瘤增强（P =.021）和肿瘤内血管的大体外观（P =.018）显著相关。KDM5C 和 BAP1 的突变与肾静脉侵犯的证据显著相关（P =.022 和 P =.046）。实性透明细胞 RCC 的基因型与多房性透明细胞 RCC 的基因型明显不同。虽然多房性透明细胞 RCC 中不存在 SETD2、KDM5C 和 BAP1 的突变，但实性透明细胞 RCC 中 VHL（P =.016）和 PBRM1（P =.017）的突变更为常见。CT 特征评估的观察者间一致性从显著到极好（κ=0.791-0.912）。
结论
这项初步的透明细胞 RCC 放射组学分析揭示了 CT 特征与潜在突变之间的关系，值得进一步研究和验证。
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