Extended Data Fig. 11: Somatic modelling of Fgfr2 variants and co-occurring driver alterations.
From: Truncated FGFR2 is a clinically actionable oncogene in multiple cancers
a-c, Kaplan-Meier curves showing mammary tumour-specific survival of Trp53F/F and Trp53F/F;Rosa26-Cas9 (a) and WT (b, c) female mice intraductally injected with lentiviruses encoding indicated variants. Trp53F/F;(Rosa26-Cas9), Lenti-Cre, sgPten–Cre, n = 10; Fgfr2FL-P2A-Cre, n = 15; Fgfr2ΔE18-P2A-Cre, sgPten–Fgfr2FL-P2A-Cre, sgPten–Fgfr2ΔE18-P2A-Cre, n = 9 mice. WT, Myc, Fgfr2FL-T2A-Fgf3, n = 9; Fgfr2FL-T2A-Myc, Fgf3, Ccnd1, Fgf3-P2A-Ccnd1, Fgfr2FL-P2A-Ccnd1, n = 10; Fgfr2ΔE18-T2A-Myc, Fgfr2ΔE18-P2A-Ccnd1, n = 7; Fgfr2FL-T2A-Fgf3-P2A-Ccnd1, n = 8; Fgfr2ΔE18-T2A-Fgf3, n = 6 mice. Fgfr2FL and Fgfr2ΔE18 curves are duplicates from Extended Data Fig. 6d. P values were calculated with log rank (Mantel-Cox) tests. ****P < 0.0001. d, Mammary tumour type classifications of somatic mouse models based on H&Es. WT, Myc, n = 30 of 9; Fgfr2FL-T2A-Myc, n = 20 of 10; Fgfr2ΔE18-T2A-Myc, Fgfr2ΔE18-P2A-Ccnd1, n = 14 of 7; Ccnd1, n = 40 of 10; Fgfr2FL-T2A-Fgf3, n = 18 of 9; Fgfr2FL-P2A-Ccnd1, Fgfr2FL-T2A-Fgf3-P2A-Ccnd1, n = 16 of 8; Fgfr2ΔE18-T2A-Fgf3, n = 12 injected MGs of 6 mice. Trp53F/F;(Rosa26-Cas9), Lenti-Cre, n = 31 of 10; Fgfr2FL-P2A-Cre, n = 14 of 7; Fgfr2ΔE18-P2A-Cre, sgPten–Fgfr2FL-P2A-Cre, sgPten–Fgfr2ΔE18-P2A-Cre, n = 18 of 9; sgPten–Cre, n = 20 injected MGs of 10 mice. WT Fgfr2FL and Fgfr2ΔE18 classifications are duplicates from Extended Data Fig. 8b. e, Histo-scoring of indicated IHC stains on mammary tumours from somatic mouse models. WT, Fgfr2FL, n = 5 of 5; Fgfr2ΔE18, n = 16 of 11; Myc, n = 7 of 3; Fgfr2FL-T2A-Myc, n = 15 of 10; Fgfr2ΔE18-T2A-Myc, n = 12 of 6; Ccnd1, n = 6 of 2; Fgfr2FL-T2A-Fgf3, n = 12 of 8; Fgfr2FL-P2A-Ccnd1, n = 14 of 9 ; Fgfr2FL-T2A-Fgf3-P2A-Ccnd1, n = 15 of 8; Fgfr2ΔE18-T2A-Fgf3, n = 12 of 7; Fgfr2ΔE18-P2A-Ccnd1, n = 13 tumours of 7 mice. Trp53F/F;(Rosa26-Cas9), Lenti-Cre, n = 10 of 8; Fgfr2FL-P2A-Cre, n = 8 of 5; Fgfr2ΔE18-P2A-Cre, n = 15 of 10; sgPten–Cre, n = 15 of 9; sgPten–Fgfr2FL-P2A-Cre, n = 14 of 7; sgPten–Fgfr2ΔE18-P2A-Cre, n = 14 tumours of 9 mice. In d, e, one tissue section per MG was stained and quantified for each of the indicated stains acquired in 4 independent randomized batches across all Fgfr2 variants and genotypes.
