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Abstract Aneuploidy is a hallmark of human cancers and studies have shown that cancer patients harbor many differences in their copy number aberrations (CNAs) reflecting interpatient heterogeneity (IPH). While IPH has been studied extensively, the intratumoral heterogeneity (ITH) of CNAs within a tumor remains understudied. Here, we conducted a pan-cancer analysis of 94 human tumor samples at single cell genomic resolution, representing seven major cancer types: bladder, breast, colon, glioblastoma, kidney, lung, and ovary. In total, 62, 646 aneuploid cells were analyzed by single cell copy number profiling and bulk exome sequencing was performed. In most cancer types, increased subclonal diversity was associated with higher CNA burden, whole genome doubling (WGD) events, and TP53 mutations. In all tumors, our data show that cancer cells share a clonal set of truncal CNAs or mutations, suggesting these tumors evolved from a single ancestral cell. In 18/94 cases we identified subclonal WGD events, which resulted in a higher number of copy number losses after tetraploidization. Macro-spatial sampling showed that increased clonal diversity also correlated with increased spatial geographical diversity. We found that many cancers evolved CNAs in short punctuated bursts of evolution, and that this was not restricted to a specific cancer type. Collectively, these data show that copy number ITH is universally associated with molecular features across these human cancer types. Citation Format: Hanghui Ye, Thomas McDonald, Emi Sei, Darlan Conterno Minussi, Min Hu, Chenling Tang, Junke Wang, Kaile Wang, Anna Casasent, Hui Chen, Franziska Michor, Nicholas Navin. A pan-cancer single-cell analysis of intratumoral copy number diversity and evolution abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 4338.
Ye et al. (Fri,) studied this question.