透明细胞肾细胞癌（ccRCC）是胰腺转移（PM）最常见的起源。 PM-ccRCC 中已报道了独特的基因组畸变、良好的预后、高血管生成的临床观察以及随后的酪氨酸激酶抑制剂 (TKI) 敏感性。然而，迄今为止尚未进行功能或单细胞研究。我们招募了 5 名 PM-ccRCC 患者，并研究了他们的患者来源细胞 (PDC) 的基因组、单细胞转录组和药物敏感性概况。 PM 描述了预期的和新的基因组改变。此外，转录组学与原发性和转移性 ccRCC 不同，PI3K/mTOR 上调，并且支持临床观察 - 血管生成途径。通路水平的数据整合表明转录组学可以最好地解释药物敏感性。因此，PM-ccRCC PDC 对许多 PI3K/mTOR 抑制剂具有敏感性。总而言之，我们在 PM-ccRCC 中展示了独特的基因组和转录组特征，强调了转录组学在解释药物敏感性方面的优越性，并鼓励在 PM-ccRCC 中使用 TKI 和 PI3K/mTOR 抑制剂。© 2024。作者。

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far. We recruited five PM-ccRCC patients and investigated the genomic, single-cell transcriptomic, and drug sensitivity profiles of their patient-derived cells (PDCs). The PM depicted both expected and novel genomic alterations. Further, the transcriptomics differed from both primary and metastatic ccRCC, with upregulations of the PI3K/mTOR and - supporting the clinical observations - angiogenesis pathways. Data integration at pathway level showed that transcriptomics explained drug sensitivities the best. Accordingly, PM-ccRCC PDCs shared sensitivity to many PI3K/mTOR inhibitors. Altogether, we show distinct genomic and transcriptomic signatures in PM-ccRCC, highlight the superiority of transcriptomics in interpreting drug sensitivities, and encourage the use of TKIs and PI3K/mTOR inhibitors in PM-ccRCC.© 2024. The Author(s).