RT Journal Article
SR Electronic
T1 Single-cell dissection of a rare human prostate basal cell carcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 818260
DO 10.1101/818260
A1 Xianbin Su
A1 Qi Long
A1 Juanjie Bo
A1 Yi Shi
A1 Li-Nan Zhao
A1 Yingxin Lin
A1 Qing Luo
A1 Shila Ghazanfar
A1 Chao Zhang
A1 Qiang Liu
A1 Lan Wang
A1 Kun-Yan He
A1 Jian He
A1 Xiao-Fang Cui
A1 Jean Y. H. Yang
A1 Ze-Guang Han
A1 Jian-Jun Sha
A1 Guoliang Yang
YR 2019
UL http://biorxiv.org/content/early/2019/10/25/818260.abstract
AB As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. Here we applied single-cell genomic amplification and RNA-Seq to a specimen of human prostate BCC (CK34βE12+/P63+/PAP−/PSA−). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the 5 putative driver genes mutated are CASC5, NUTM1, PTPRC, KMT2C and TBX3. The top 3 nucleotide substitutions are C>T, T>C and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated these single cells are from the same tumor clone. The transcriptomes of 69 single cells were obtained, and they were clustered into tumor, stromal and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14 and KRT23, and epithelial markers EPCAM, CDH1 and CD24. The transcription factor (TF) co-variance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal-cell signatures. Interestingly, at single-cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer-derived circulating tumor cells. This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.