APC and neoplasm: Another ‘hit’ in the APC tumour suppressor, a Wnt pathway negative regulator altered in 20% of CIN GC (Extended Data Fig. 2a), was concurrently engineered in C2 and C3 from D3 (referred to as D3C2 and D3C3, respectively; Supplementary Figs. 1 and 3) to examine the evolutionary consequence of dual tumour suppressor inactivation.