Gene

Biology

Cell culture

Cancer research

Neuroblastoma

Genetics

Transcriptome

Cell

Neural crest

Cancer

Gene expression

Cancer cell

Phenotype

Science Advances

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer ( n = 19,723) with normal fetal adrenal single-cell transcriptomes ( n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.

Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell