Background/Objectives:KRASmutations in renal cell carcinoma (RCC) are uncommon and most frequently described in papillary renal neoplasm with reverse polarity (PRNRP). Beyond this entity, the broader clinicopathologic and molecular features ofKRAS-mutated RCC remain insufficiently characterized. This study aimed to provide a descriptive assessment ofKRAS-mutated RCC. Methods:KRAS-mutant RCC patients were identified from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) and The Cancer Genome Atlas Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) cohorts. Copy-number alterations were evaluated using Fraction and allele-specific copy number estimates from tumor sequencing (FACETS). Available samples were used for immunohistochemistry and RNA-sequencing analysis. Results: Seventeen patients were included. Three distinctKRAS-mutant RCC subtypes were identified:KRAS-mutant PRCC (35%),KRAS-mutant URCC (35%), and PRNRP (29%). Seven patients (41%) had metastatic disease; none were PRNRP. RNA-based deconvolution analysis revealed that PRNRP had enrichment in distal nephron components, whereasKRAS-mutant PRCC was enriched in proximal tubule cells (p= 0.02). IHC staining of L1CAM was positive in PRNRP but negative inKRAS-mutant PRCC, supporting their distinct cell-of-origin phenotypes. This study is limited by its cohort size, which influences the availability of tissue samples. Conclusions: PRNRP represents a distinctKRAS-mutant RCC subtype with unique metabolic and genomic features linked to its distal nephron origin. This contrasts with the genomic complexity and aggressive clinical behavior observed inKRAS-mutant PRCC and URCC, highlighting the need for subtype-specific diagnostic criteria and therapeutic strategies.
背景/目的：肾细胞癌（RCC）中的KRAS突变并不常见，最常见于具有反向极性的乳头状肾肿瘤（PRNRP）。除该病种外，KRAS突变型RCC更广泛的临床病理和分子特征仍未得到充分描述。本研究旨在对KRAS突变型RCC进行描述性评估。方法：从纪念斯隆凯特琳癌症中心可操作癌症靶点综合突变谱分析（MSK-IMPACT）队列和癌症基因组图谱肾乳头状细胞癌（TCGA-KIRP）队列中识别KRAS突变型RCC患者。使用肿瘤测序的片段等位基因特异性拷贝数评估（FACETS）方法评估拷贝数变异。可用样本用于免疫组织化学和RNA测序分析。结果：共纳入17例患者。确定了三种不同的KRAS突变型RCC亚型：KRAS突变型乳头状肾细胞癌（PRCC）（35%）、KRAS突变型未分类肾细胞癌（URCC）（35%）和PRNRP（29%）。7例患者（41%）发生转移性疾病；无一例为PRNRP。基于RNA的反卷积分析显示，PRNRP在远端肾单位成分中富集，而KRAS突变型PRCC在近端肾小管细胞中富集（p=0.02）。L1CAM的免疫组化染色在PRNRP中呈阳性，而在KRAS突变型PRCC中呈阴性，支持其不同的细胞起源表型。本研究受限于队列规模，这影响了组织样本的可获得性。结论：PRNRP代表了一种独特的KRAS突变型RCC亚型，具有与其远端肾单位起源相关的独特代谢和基因组特征。这与在KRAS突变型PRCC和URCC中观察到的基因组复杂性和侵袭性临床行为形成对比，凸显了制定亚型特异性诊断标准和治疗策略的必要性。
Clinical and Molecular Characterization of KRAS-Mutated Renal Cell Carcinoma
肿瘤(癌症)患者之家