Spatial architectures of somatic mutations in normal prostate, benign prostatic hyperplasia and coexisting prostate cancer

被引:1
作者
Chae, Jeesoo [1 ,2 ]
Jung, Seung-Hyun [3 ,4 ,5 ]
Choi, Eun Ji [6 ]
Kim, Jae Woong [5 ,6 ]
Kim, Na Yung [5 ]
Moon, Sung Won [5 ,6 ]
Lee, Ji Youl [7 ]
Chung, Yeun-Jun [1 ,4 ,5 ,8 ]
Lee, Sug Hyung [1 ,5 ,6 ]
机构
[1] Catholic Univ Korea, Coll Med, Dept Canc, Evolut Res Ctr, Seoul 06591, South Korea
[2] Ewha Womans Univ, Coll Med, Dept Biochem, Seoul 07804, South Korea
[3] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 06591, South Korea
[4] Catholic Univ Korea, Coll Med, Integrated Res Ctr Genome Polymorphism, Seoul 06591, South Korea
[5] Catholic Univ Korea, Coll Med, Dept Biomed & Hlth Sci, Seoul 06591, South Korea
[6] Catholic Univ Korea, Coll Med, Dept Pathol, Seoul 06591, South Korea
[7] Catholic Univ Korea, Coll Med, Dept Urol, Seoul 06591, South Korea
[8] Catholic Univ Korea, Coll Med, Dept Microbiol, Seoul 06591, South Korea
基金
新加坡国家研究基金会;
关键词
SIGNATURES; DYNAMICS; DNA;
D O I
10.1038/s12276-023-01140-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes. The study explores the genetic differences between regular prostate cells, benign prostatic hyperplasia (non-cancerous enlargement of the prostate) cells, and prostate cancer cells. The researchers found that regular and benign prostatic hyperplasia cells are more alike than they are to prostate cancer cells. Using whole-genome sequencing, they discovered that benign prostatic hyperplasia cells had a higher rate of genetic changes, more clonal expansion, and more subclonal somatic mutations than regular cells. However, the difference was small, suggesting that benign prostatic hyperplasia is a non-cancerous disease. The study also found no link between somatic mutations and prostate cancer development. These findings offer valuable insights into the cell characteristics of benign prostatic hyperplasia and its connection with prostate cancer. Further studies are required to understand the clinical importance of these genetic features. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
引用
收藏
页码:168 / 176
页数:9
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