Conserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-09 DOI:10.1016/j.celrep.2024.115169

Olivia Lombardi, Ran Li, Faiz Jabbar, Hannah Evans, Silvia Halim, Joanna D C C Lima, Lisa Browning, Helen M Byrne, Hani Choudhry, Peter J Ratcliffe, David R Mole

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引用次数: 0

Abstract

Clear cell kidney cancers are characterized both by conserved oncogenic driver events and by marked intratumor genetic and phenotypic heterogeneity, which help drive tumor progression, metastasis, and resistance to therapy. How these are reflected in transcriptional programs within the cancer and stromal cell components remains an important question with the potential to drive novel therapeutic approaches to treating cancer. To better understand these programs, we perform single-cell transcriptomics on 75 multi-regional biopsies from kidney tumors and normal kidney. We identify conserved patterns of transcriptional dysregulation and their upstream regulators within the tumor and associated vasculature. We describe recurrent subclonal transcriptional consequences of Chr14q loss linked to metastatic potential. We identify prognostically significant conserved patterns of intratumor transcriptional heterogeneity. These reflect co-existing cell states found in both cancer cells and normal kidney cells, indicating that rather than arising from genetic heterogeneity they are a consequence of lineage plasticity.

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透明细胞肾癌中转录失调、异质性和细胞状态的保守模式。

透明细胞肾癌的特点是保守的致癌驱动事件和显著的肿瘤内遗传和表型异质性，这有助于驱动肿瘤进展、转移和对治疗的抵抗。这些如何反映在癌症和基质细胞成分的转录程序中仍然是一个重要的问题，有可能推动新的治疗方法来治疗癌症。为了更好地理解这些程序，我们对75例来自肾脏肿瘤和正常肾脏的多区域活检进行了单细胞转录组学。我们确定了肿瘤和相关脉管系统中转录失调的保守模式及其上游调节因子。我们描述了与转移潜能相关的Chr14q缺失的复发性亚克隆转录后果。我们确定了具有预后意义的肿瘤内转录异质性的保守模式。这些反映了癌细胞和正常肾细胞中共存的细胞状态，表明它们不是由遗传异质性引起的，而是谱系可塑性的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.