Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.
膀胱尿路上皮癌（BLCA）是第十大常见癌症，其生存率较低且具有显著的男性偏向性。本研究采用每位患者多样本、多组织的方案，旨在敏感检测常染色体合子后染色体改变及Y染色体缺失（LOY），以探究BLCA中的区域癌化现象。我们利用自主优化的嵌合染色体改变（MoChA）分析流程，对来自52名男性和15名女性的277份组织学正常尿路上皮样本、145份肿瘤样本及63份血液样本进行了分析。该方法能够识别BLCA患者尿路上皮中的早期遗传异常。总体而言，45%的患者在至少一份正常尿路上皮样本中表现出至少一种遗传改变。复发分析确定了16个热点区域，这些区域包含增益与拷贝数中性杂合性缺失（CN-LOH）或缺失与CN-LOH的组合，涵盖了已知及新发现的BLCA癌症驱动基因。对LOY的保守评估显示，肿瘤、血液和正常尿路上皮中分别存在29%、27%和18%的LOY细胞。本研究从原理上证明，我们的方法能够表征促使正常尿路上皮向BLCA发展的最早阶段遗传改变。血液和尿路上皮来源组织中频繁出现的LOY现象提示其可能参与BLCA的发生发展。
肿瘤(癌症)患者之家