评估透明细胞肾细胞癌 (ccRCC) 中不同肿瘤大小的关键突变的分布，其次检查较小 ccRCC 中侵袭性突变的预后影响。突变的分布（VHL、PBRM1、SETD2、BAP1 和 CDKN2A 丢失） ）在从跟踪癌症进化（TRACERx）、癌症基因组图谱（TCGA）和肾脏癌症基因组学（CAGEKID）项目获得的队列中，对 1039 个接受肾切除术治疗的 ccRCC 进行了肿瘤大小的评估。使用逻辑回归对每个突变的存在与大小进行建模。在我们的二次分析中，我们评估了 ≤7cm 的 ccRCC 子集，以确定关键侵袭性突变（SETD2、BAP1 和 CDKN2A 缺失）与转移、侵袭性疾病和总体生存率的关联，同时控制了大小。 ≤7cm 的局部肿瘤子集也被用来评估与肾切除术后复发的关联。在逻辑回归中，肿瘤大小每增加 1cm 就与侵袭性突变、SETD2、BAP1 和 CDKN2A 丢失相关，比值比 (ORs) ）分别为 1.09、1.10 和 1.19（P < 0.001），而肿瘤大小与 PBRM1 之间没有观察到显着相关性（OR 1.02；P = 0.23）。 VHL 与尺寸增加 1 厘米呈轻度负相关（OR 0.95；P = 0.01）。在≤7cm的肿瘤中，在控制肿瘤大小的情况下，SETD2和CDKN2A缺失与转移性疾病相关，OR分别为3.86和3.84（P<0.05）。 CDKN2A 缺失与较差的总生存率相关，风险比 (HR) 为 2.19 (P = 0.03)。在≤7cm的局部肿瘤中，SETD2与较差的无复发生存率相关（HR 2.00；P = 0.03）。大型和小型ccRCC在基因组上存在差异。侵袭性突变，即 SETD2、BAP1 和 CDKN2A 缺失，在小型 ccRCC 中很少观察到，而在较大的肿瘤中更常见。然而，当肿瘤≤7cm时，在控制大小后，SETD2突变和CDKN2A缺失仍然与侵袭性疾病、转移、较差的生存率和切除后复发独立相关。© 2024 作者。 BJU International 约翰·威利 (John Wiley) 出版

To assess the distribution of key mutations across tumour sizes in clear-cell renal cell carcinoma (ccRCC), and secondarily to examine the prognostic impact of aggressive mutations in smaller ccRCCs.The distribution of mutations (VHL, PBRM1, SETD2, BAP1 and CDKN2A loss) across tumour sizes was assessed in 1039 ccRCCs treated with nephrectomy in cohorts obtained from the Tracking Cancer Evolution (TRACERx), The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) projects. Logistic regression was used to model the presence of each mutation against size. In our secondary analysis, we assessed a subset of ccRCCs ≤7 cm for associations of key aggressive mutations (SETD2, BAP1, and CDKN2A loss) with metastasis, invasive disease and overall survival, while controlling for size. A subset of localised tumours ≤7 cm was also used to assess associations with recurrence after nephrectomy.On logistic regression, each 1-cm increase in tumour size was associated with aggressive mutations, SETD2, BAP1, and CDKN2A loss, at odds ratios (ORs) of 1.09, 1.10 and 1.19 (P < 0.001), whereas no significant association was observed between tumour size and PBRM1 (OR 1.02; P = 0.23). VHL was mildly negatively associated with a 1-cm increase in size (OR 0.95; P = 0.01). Among tumours ≤7 cm, SETD2 and CDKN2A loss were associated with metastatic disease at ORs of 3.86 and 3.84 (P < 0.05) while controlling for tumour size. CDKN2A loss was associated with worse overall survival, with a hazard ratio (HR) of 2.19 (P = 0.03). Among localised tumours ≤7 cm, SETD2 was associated with worse recurrence-free survival (HR 2.00; P = 0.03).Large and small ccRCCs are genomically different. Aggressive mutations, namely, SETD2, BAP1, and CDKN2A loss, are rarely observed in small ccRCCs and are observed more frequently in larger tumours. However, when present in tumours ≤7 cm, SETD2 mutations and CDKN2A loss were still independently associated with invasive disease, metastasis, worse survival, and recurrence after resection, after controlling for size.© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.