Fig. 5
DNA damage repair signatures before and after PIKTOR treatment. (A) Mutational signatures of DNA damage repair using COSMIC v3 Mutation Signature. SBS signature ID is highlighted, and presence of DNA damage repair defect is indicated by filled space in table. (B) Oncoprint of somatic variants and copy number alterations to genes involved in DNA repair and associated chromatin remodeling. Pre/Post samples are designated by white and black circles, respectively. Variant or copy number alteration is designated as represented in the legend. ND = not determinable for copy number. (C) Unsupervised hierarchical clustering levels of DNA damage repair pathway proteins in microdissected lymph node metastasis reveals heterogeneous signaling profiles. Pre and post samples are represented by white and black triangles, respectively. (D) Biological signaling pathway superimposed with log2 fold changes in average protein levels pre-PIKTOR compared to post-PIKTOR. Patients with lymph node metastasis biopsy specimens both pre and post-PIKTOR were 1, 4, 6, 8,10 and 11. Sample 2 was excluded from analysis because the pre and post biopsy were from different metastatic sites (lung and lymph node). (E) Phosphorylation of Rb allows cell cycle progression. Increased levels of phosphorylated Rb protein in responders post PIKTOR treatment may sensitize cells to DNA damaging therapies such as cisplatin. Only patient #6 had a Rb gene mutation in the pre-PIKTOR sample