■原发性透明细胞肾细胞癌(ccRCC)的肾切除术后复发的风险仅根据临床标准在日常实践中进行估计。这项研究的目的是评估常见体细胞突变与明确治疗后ccRCC患者的肿瘤侵袭性和预后的相关性。
■使用15基因靶向下一代测序(NGS)小组分析了37例接受根治性肾切除术的ccRCC患者的原发性肿瘤是否存在体细胞突变。在研究队列(n=37)中调查了与组织病理学特征和结果的关联,并在癌症基因组图谱(TCGA)ccRCC队列(n=451)中进行了验证。
■VHL是最常见的突变基因(51%),其次是PBRM1(27%),BAP1(13%),SETD2(13%),KDM5C(5%),ATM(5%),MTOR(5%),和PTEN(3%)。三分之一的患者在15个基因组中没有任何体细胞突变。绝大多数完全没有突变或VHL突变(51%)的肿瘤更常见的是较小的大小(pT1-2)和早期(I/II),而有或没有VHL的各种组合中任何其他基因突变的存在在较大(pT3)和较高分期(III)的肿瘤中富集(p=0.02).在具有未突变的肿瘤或仅VHL突变的患者中没有发现复发,而在具有非VHL体细胞突变的患者中没有发现3次复发(p=0.06)。PBRM1,BAP1,SETD2,KDM5C中存在体细胞突变,ATM,MTOR,451名TCGAccRCC患者中的PTEN基因与肿瘤未改变的患者相比,无病生存期(DFS)显着缩短(q=0.01)。
■这项正在进行的研究的初步发现支持非VHL突变的预后价值,包括PBRM1,BAP1,SETD2,KDM5C,ATM,MTOR,和PTEN在原发性ccRCC肿瘤中作为早期复发的替代和辅助免疫检查点抑制的潜在选择。
UNASSIGNED: The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment.
UNASSIGNED: Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451).
UNASSIGNED: VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non- VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01).
UNASSIGNED: Preliminary findings from this ongoing study support the prognostic value of non- VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.