Lineage plasticity and immune cell heterogeneity are coordinately dysregulated through changes in FOXA1 expression in bladder cancers with squamous differentiation

We performed whole exome sequencing (WES) of paired, macrodissected regions of urothelial carcinoma (UC), not otherwise specified (NOS-UC) and squamous differentiation (SqD) from 21 bladder tumors in which distinct and separable NOS-UC and SqD regions were present (total 42 exomes, in addition to matched normal exomes). Mean tumor mutational burden (TMB) was higher in the SqD versus the NOS-UC regions. Consistent with the higher TMB, the SqD regions also had a higher neoantigen burden than the patient-matched NOS-UC regions. The SqD regions also exhibited higher karyotypic complexity with a higher median ploidy relative to the paired NOS-UC regions. Phylogenetic analysis of the WES data confirmed that the morphologically distinct regions of all 21 tumors arose from a shared precursor... (for more see dbGaP study page.)

我们针对21例同时存在可区分且可分离的非特指型尿路上皮癌（urothelial carcinoma, not otherwise specified, NOS-UC）与鳞状分化（squamous differentiation, SqD）区域的膀胱肿瘤，对其配对的宏观解剖分离区域开展了全外显子组测序（whole exome sequencing, WES），共获得42例外显子组数据，同时还配套获取了配对正常组织的外显子组数据。鳞状分化区域的平均肿瘤突变负荷（tumor mutational burden, TMB）显著高于非特指型尿路上皮癌区域。与更高的肿瘤突变负荷相契合，鳞状分化区域的新抗原负荷同样高于患者配对的非特指型尿路上皮癌区域。相较于配对的非特指型尿路上皮癌区域，鳞状分化区域还呈现出更高的核型复杂度，中位倍性更高。对上述全外显子组测序数据进行的系统发育分析证实，全部21例肿瘤的形态学差异区域均源自共同的前体（更多详情请参见dbGaP研究页面）。