Fig 4.

(A) Tumor progression in an index patient with adenoid cystic carcinoma (ACC) was associated with the sequential identification of multiple mutations in the Notch1 pathway. The peripheral blood sample showed wild-type sequence at all NOTCH1 amplicons/codons covered by the assay. (B) Tumor from index patient with NOTCH1-mutant ACC was strongly positive for Notch1 intracellular domain by immunohistochemistry. (C) Patient with NOTCH1-mutant ACC achieved a partial response with a 38% reduction in the target lesion upon treatment with two doses of the anti-Notch1 monoclonal antibody brontictuzumab. CAP, cyclophosphamide, doxorubicin, and cisplatin; Carbo, carboplatin; ISIS482464, STAT3 inhibitor administered under a phase I clinical trial protocol; VAF, variant allele frequency. (†) No tumor available for genotyping. (‡) Genotyping performed in cell-free DNA.