A pan-organ single-cell atlas of somatic copy-number variation in human

Cancer is fundamentally an evolutionary process driven by the accumulation of somatic alterations enabling cells to escape normal growth barriers. Over the past years, sequencing has profoundly reshaped our view on tumorigenesis, revealing the landscape of driver mutations, mutational processes, and selective pressures that shape tumor evolution. Recent discoveries on normal tissues have shown that they do also accumulate substantial somatic mutations including well-known cancer drivers. This discovery has challenged the traditional boundaries between healthy and malignant states, suggesting that the earliest steps toward cancer may begin within normal tissues.Although aneuploidy has long been recognized as a hallmark of cancer and is present in the majority of solid tumors, it has also traditionally been viewed as a feature restricted to malignant cells arising from chromosomal instability. Recent advances in single-cell genomic profiling have begun to overturn this notion. Studies have shown that even histologically normal and non-malignant tissues can harbor rare populations of aneuploid cells. These observations fundamentally challenge the traditional dichotomy between normal and cancer genomes. This project aims to uncover the fundamental mutational and selective processes that control chromosomal alterations in normal human tissues. By mapping copy-number aberrations at single-cell resolution across multiple organs, it will provide the first comprehensive, pan-organ view of somatic chromosomal variation. This approach will illuminate how tissue-specific contexts influence the emergence, tolerance, and expansion of aneuploid cells. The resulting atlas of normal somatic chromosomal alterations will constitute a foundational resource for the field, offering a new lens through which we could observe and understand the earliest molecular events preceding malignant transformation. Ultimately, these insights will advance our understanding of the continuum from normal tissue homeostasis to cancer initiation.

Keywords:Atlas, somatic copy-number variation, pan-organ, cancer, single-cell

Disciplines:Analysis of next-generation sequence data, Single-cell data analysis, Computational transcriptomics and epigenomics, Bioinformatics of disease, Bioinformatics data integration and network biology, Cancer biology

Project type:PhD project