Im Sun-Wha, Sung Chang Ohk, Kim Kun Suk, Cho Nam Hoon, Kim Young Min, Kwon Ghee Young, Moon Kyung Chul, Choi Song-Yi, Lim Jae Sung, Choi Yeong Jin, Jung Soo Jin, Lim So Dug, Paick Sung Hyun, Lee Ok-Jun, Kang Ho Won, Rha Seo Hee, Hwang Hee Sang, Park Ja-Min, Yoon Sun Young, Chae Jeesoo, Choi Jaeyong, Kim Jong-Il, Cho Yong Mee
Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Cancers (Basel). 2020 Jan 28;12(2):307. doi: 10.3390/cancers12020307.
Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age.
由于年轻发病的膀胱癌（YBC）发病率较低，其基因组特征在很大程度上仍不清楚。通过全国范围内搜索20岁及以下诊断出的膀胱癌，收集了29例经活检证实的YBC病例。分别对21例和11例进行了全外显子组测序和RNA测序，并与从公共数据库中获得的成人膀胱癌（ABC）病例进行了比较。几乎所有YBC均为低级别、非侵袭性乳头状肿瘤。YBC的突变负担较低，拷贝数改变的复杂性也较低。所有病例均存在假定的驱动突变。突变最常见于HRAS（10例），且偏好于第5外显子。发现FGFR3基因与各种伙伴基因发生融合（7例）。HRAS和FGFR3的改变以相互排斥的方式发生。其他包括KRAS突变（2例）、4号染色体短臂和10号染色体长臂水平缺失（1例）以及ERCC2突变（1例）。TP53和FGFR3未发现点突变。YBC的基因表达谱与预后良好的ABC组相似。没有YBC和具有YBC样突变的ABC进展为肌层浸润性肿瘤。我们的结果表明，具有YBC样突变类型的膀胱癌代表一种惰性膀胱肿瘤，与年龄无关。
