透明细胞肾细胞癌中肿瘤大小的突变差异
Differences in mutations across tumour sizes in clear-cell renal cell carcinoma
影响因子:4.40000
分区:医学2区 / 泌尿学与肾脏学2区
发表日期:2025 Feb
作者:
Steven M Monda, Benjamin W Carney, Allison M May, Shuchi Gulati, Simpa S Salami, Thenappan Chandrasekar, Evan T Keller, Nicolai A Huebner, Ganesh S Palapattu, Marc A Dall'Era
摘要
要评估透明细胞肾细胞癌（CCRCC）跨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，Bap1和CDKN2A损失）在1039 ccrccs ccrccs ccrccs ccrccs ccrcce ccrcce ccrcce ccrcce ccrcce ccrccs ccrccs ccrccs ccrccs ccrccs ccrccs ccrccs进行了评估。 （Tracerx），癌症基因组图集（TCGA）和肾脏（Cagekid）项目的癌症基因组学。逻辑回归用于建模每个突变与大小的存在。在我们的次要分析中，我们评估了CCRCC≤7cm的子集，用于与转移，侵入性疾病和整体存活的关键侵袭性突变（SETD2，BAP1和CDKN2A损失）的关联，同时控制大小。 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与大小增加1厘米（或0.95; p = 0.01）有轻度负相关。在控制肿瘤大小的同时，在≤7cm的肿瘤≤7cm中，SETD2和CDKN2A损失与3.86和3.84（P <0.05）的转移性疾病有关。 CDKN2A损失与较差的总生存期有关，危险比（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有关（HR 2.00； P = 0.03）。LARGE，小CCRCC在基因组上不同。在小CCRCC中很少观察到侵略性突变，即SetD2，Bap1和CDKN2A丢失，在较大的肿瘤中观察到更频繁的观察到。但是，当存在≤7cm的肿瘤中时，SETD2突变和CDKN2A损失仍然与侵入性疾病，转移，生存率较差和切除后复发相关，在控制大小后。
Abstract
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.