Fig. 2. Phylogeny of early EAC and precursor BE lesions within a single BE field from each patient determined by haplotype-specific copy-number alterations.

For a comparison against single-nucleotide-mutation derived phylogeny, see Supplementary Fig. 2 and Supplementary Information. Phylogenetic trees are grouped based on the timing of whole-genome duplication (WGD, thick solid line). Samples are colored based on their histopathology grading: blue for non-dysplastic BE (BE) or BE indefinite for dysplasia (IND), orange for low-grade dysplasia (LGD), red for high-grade dysplasia (HGD), and magenta for carcinoma (EAC or IMEAC). Samples with both HGD and IMEAC features are annotated as HGD/IM. The branch length (horizontal distance between nodes) approximately reflects the number of altered chromosomes. For a complete list of alterations along each evolutionary branch, see Supplementary Data 2. Annotated alterations include: (1) recurrent alterations or those affecting known EAC drivers; (2) focally amplified regions or oncogenes (magenta); (3) chromosomes or chromosome arms (with asterisks) with divergent copy-number alterations in more than one progeny clones. Note that patient 13 contained a splice-site mutation (c.375+5 G > C) in TP53 that was assessed to produce truncated p53⁶⁴ and also reported to be a recurrent mode of p53 inactivation in cancers⁶⁵. The colors of annotated chromosomes reflect the complexity of copy-number alterations: simple deletion/duplication, uniparental disomy, arm-level gain/loss (blue), large segmental (terminal or internal) copy-number changes or their combinations (orange), complex copy-number alterations (red), focal amplifications (magenta). For classification of copy-number alterations, see Supplementary Fig. 4.