Fig. 2: Some FAP premalignant polyps had an early most recent common evolutionary ancestor and are probably polyclonal.

a, Schematic showing that polyclonal polyps are initiated from several colorectal crypts in the intestinal mucosa (green crypts), whereas monoclonal polyps are the result of a clonal expansion of a single crypt (pink). b, Schematic showing that monoclonal lesions have an MRCA occurring after lesion initiation (dotted line) because they initiate from a single crypt, leading to many detected clonal mutations (purple Xs on tree). Bottom parts show hypothetical ppVAF distribution shapes for monoclonal and polyclonal samples, with clonal mutations marked in purple. c, Number of expected clonal SNVs detected in WGS data from samples from patients with FAP. Samples with fewer than 63 clonal SNVs (dashed line, corresponding to an MRCA at less than 1 year old) were classified as having an early MRCA and are probably polyclonal. d, ppVAF distributions for example monoclonal (left) and polyclonal (right) lesions. e, ppVAF distributions for all monoclonal (left) and polyclonal (right) lesions combined. f, Fraction of WGS samples classified as polyclonal based on estimated clonal SNV count. Fractions were estimated from n = 25 mucosal samples, n = 15 benign polyp samples and n = 54 dysplastic polyp samples. Error bars are 95% Bayesian credible intervals (Supplementary Methods). Illustrations in a were created using BioRender. Ma, Z. (2025) https://BioRender.com/4v5zpca.