Department of Pathology, Beijing Hospital, National Center of Gerontology, Beijing, China; The Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
Department of Pathology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Eur Urol. 2018 Nov;74(5):551-559. doi: 10.1016/j.eururo.2018.06.005. Epub 2018 Jun 23.
Prostate adenocarcinoma (PCa) is a complex genetic disease, and the implementation of personalized treatment in PCa faces challenges due to significant inter- and intrapatient tumor heterogeneities.
To systematically explore the genomic complexity of tumor cells with different Gleason scores (GSs) in PCa.
DESIGN, SETTING, AND PARTICIPANTS: We performed single-cell whole genome sequencing of 17 tumor cells from localized lesions with distinct GS and matched four normal samples from two prostatectomy patients.
All classes of genomic alterations were identified, including substitutions, insertions/deletions, copy number alterations, and rearrangements.
Significant spatial, intra- and intertumoral heterogeneities were observed at the cellular level. In the patient 1, all cells shared the same TP53 driver mutation, implying a monoclonal origin of PCa. In the patient 2, only a subpopulation of cells contained the TP53 driver mutation, whereas other cells carried different driver mutations, indicating a typical polyclonal model with separate clonal cell expansions. The tumor cells from different sides of prostate owned various mutation patterns. Considerable neoantigens were predicted among different cells, implying unknown immune editing components helping prostate tumor cells escaping from immune surveillance.
There is a significant spatial genomic heterogeneity even in the same PCa patient. Our study also provides the first genome-wide evidence at single-cell level, supporting that the origin of PCa could be either polyclonal or monoclonal, which has implications for treatment decisions for prostate cancer.
We reported the first single-cell whole genomic data of prostate adenocarcinoma (PCa) from different Gleason scores. Identification of these genetic alterations may help understand PCa tumor progression and clonal evolution.
前列腺腺癌（PCa）是一种复杂的遗传疾病，由于肿瘤内和肿瘤间存在显著的异质性，PCa 的个性化治疗实施面临挑战。
系统探索具有不同 Gleason 评分（GS）的 PCa 肿瘤细胞的基因组复杂性。
设计、设置和参与者：我们对来自两名前列腺切除术患者的 4 个匹配正常样本和 2 个具有不同 GS 的局灶性病变的 17 个肿瘤细胞进行了单细胞全基因组测序。
鉴定了所有类别的基因组改变，包括替换、插入/缺失、拷贝数改变和重排。
在细胞水平上观察到显著的空间、肿瘤内和肿瘤间异质性。在患者 1 中，所有细胞都携带相同的 TP53 驱动突变，表明 PCa 为单克隆起源。在患者 2 中，只有部分细胞携带 TP53 驱动突变，而其他细胞携带不同的驱动突变，表明存在典型的多克隆模型，存在单独的克隆细胞扩增。来自前列腺不同侧的肿瘤细胞具有不同的突变模式。不同细胞预测到大量的新生抗原，表明存在未知的免疫编辑成分帮助前列腺肿瘤细胞逃避免疫监视。
即使在同一个 PCa 患者中，也存在显著的空间基因组异质性。我们的研究还提供了单细胞水平全基因组证据，支持 PCa 的起源可能是多克隆或单克隆，这对前列腺癌的治疗决策具有重要意义。
我们报告了首例来自不同 Gleason 评分的前列腺腺癌（PCa）的单细胞全基因组数据。这些遗传改变的鉴定可能有助于理解 PCa 肿瘤的进展和克隆演变。
