Background

Papillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for advanced PRCC.

Objective

To characterize the frequency of genomic alterations (GAs) in patients with advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the context of routine clinical care.

Design, setting, and participants

Formalin-fixed, paraffin-embedded tissue was obtained for 169 consecutive patients with confirmed PRCC. DNA was extracted and comprehensive genomic profiling was performed in a certified central laboratory.

Measurements

Hybrid-capture, adaptor ligation-based libraries of up to 315 genes were sequenced to a median coverage of 648×. All classes of GAs were identified, including substitutions, insertions/deletions, copy number alterations, and rearrangements.

Results and limitations

From 169 patients, either primary tumor tissue (102 patients, 60%) or metastatic tissue (67 patients, 40%) was collected. In patients with type 1 PRCC, commonly altered genes were MET (33%; 8 activating mutations, 5 amplifications at > 6 copies), TERT (30%), CDKN2A/B (13%), and EGFR (8%). In patients with type 2 PRCC, commonly altered genes were CDKN2A/B (18%), TERT (18%), NF2 (13%), and FH (13%); MET GAs (5 mutations, 3 amplifications) were observed in 7% of type 2 cases. Notable differences from TCGA data include higher frequencies of MET, NF2, and CDKN2A/B GAs, association of alterations in SWI/SNF complex genes with type 2 PRCC, and observation of frequent CDKN2A/B alterations in both type 1 and type 2 disease.

Conclusions

Both the current study and the TCGA experience represent similarly sized cohorts of patients with PRCC. Key differences in GA frequency probably underscore the marked difference in stage distribution between these data sets. These results may inform planned precision medicine trials for metastatic PRCC.

Patient summary

Papillary renal cell carcinoma (PRCC) is a rare subtype of kidney cancer, and understanding of the biology of advanced PRCC is limited. This report highlights some of the unique biologic features of PRCC that may inform on future use of targeted therapies for the treatment of metastatic disease.

中文翻译：

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通过全面的基因组分析表征晚期乳头状肾细胞癌的临床病例

背景

乳头状肾细胞癌（PRCC）是RCC的罕见子集。癌症基因组图谱（TCGA）数据在很大程度上反映了局部疾病，晚期PRCC的数据有限。

客观的

为了表征在常规临床护理中进行了全面基因组概况分析（CGP）的晚期PRCC患者的基因组改变（GAs）的频率。

设计，设置和参与者

连续169例确诊为PRCC的患者获得了福尔马林固定，石蜡包埋的组织。提取DNA，并在经过认证的中央实验室中进行全面的基因组分析。

测量

对多达315个基因的基于杂交捕获，基于衔接子连接的文库进行测序，得出中位覆盖率为648x。确定了GA的所有类别，包括替代，插入/缺失，拷贝数变更和重排。

结果与局限性

从169例患者中，收集了原发性肿瘤组织（102例患者，占60％）或转移性组织（67例患者，占40％）。在患有1型PRCC的患者中，通常改变的基因是MET（33％； 8个激活突变，> 6个拷贝的5个扩增），TERT（30％），CDKN2A / B（13％）和EGFR（8％）。在患有2型PRCC的患者中，通常改变的基因是CDKN2A / B（18％），TERT（18％），NF2（13％）和FH（13％）。在7％的2型病例中观察到MET GAs（5个突变，3个扩增）。与TCGA数据的显着差异包括较高的MET，NF2和CDKN2A / B GA，SWI / SNF复杂基因的改变与2型PRCC的关联以及在1型和2型疾病中频繁出现CDKN2A / B改变的观察。

结论

当前的研究和TCGA经验均代表了类似规模的PRCC患者队列。GA频率的关键差异可能突显了这些数据集之间的阶段分布显着差异。这些结果可能为计划中的转移性PRCC精密医学试验提供依据。

病人总结

乳头状肾细胞癌（PRCC）是一种罕见的肾癌亚型，对晚期PRCC生物学的理解是有限的。本报告重点介绍了PRCC的一些独特生物学特性，这些信息可能会为将来靶向治疗转移性疾病提供参考。