Molecular Dissection of Complete Response to Receptor Tyrosine Kinase Inhibition in Type II Papillary Renal Cell Carcinoma Matti Annala, Lucia Nappi,

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Molecular Dissection of Complete Response to Receptor Tyrosine Kinase Inhibition in Type II Papillary Renal Cell Carcinoma Matti Annala, Lucia Nappi, Arun A. Azad, Fan Mo, Ladan Fazli, Kim N. Chi, Alexander W. Wyatt Clinical Genitourinary Cancer Volume 15, Issue 1, Pages e145-e150 (February 2017) DOI: 10.1016/j.clgc.2016.05.019 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Complete Response to Receptor Tyrosine Kinase Inhibition. (A) CT Scan Demonstrating the Primary Kidney Mass in the Index Patient. (B) Hematoxylin and Eosin Stains of the Primary Tumor Showing Features Consistent With Type II Papillary Renal Cell Carcinoma. (C) CT Scans Over the Initial 12 Months of (Sunitinib Treatment Demonstrating Resolution of Metastatic Disease. (D) Ovary Metastasis That Developed After Sunitinib Dose Was Reduced. (E) Tumor Relapse on the Left Adrenal Gland Requiring Adrenalectomy. (F) Evidence of Multiple Uterine Fibroids Consistent With HLRCC. (G) CT Scans again Showing Resolution of Metastatic Disease after Therapy Switch to Pazopanib Abbreviations: CT = computed tomography; HLRCC = hereditary leiomyomatosis and renal cell cancer. Clinical Genitourinary Cancer 2017 15, e145-e150DOI: (10.1016/j.clgc.2016.05.019) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 Landscape of Mutations and Copy Number Alterations. (A) Summary of Key Genomic Changes Detected by Exome Sequencing in the Index Case With Complete Response to RTK Inhibition (Left 2 Columns), and the 4 Other Type II pRCC Cases With Typical Poor Response to Therapy. (B) Copy Number Profiles for All 5 Cases With Key Altered Genes Annotated. Note the Similarity of the Primary Tumor and Ovary Metastasis for the Index Case (Top 2 Profiles). (C) Evidence of Somatic Loss of Heterozygosity for Germline FH Mutation, but Not the Germline FANCM Mutation in the Index Case. Location of the FH Mutation is Annotated on a Protein Domain Schematic. (D) Plot Showing that the Ovary Metastasis in the Index Case Harbors all the Mutations that Were Detected in the Primary Tumor Abbreviations: FH = fumarate hydratase; pRCC = papillary renal cell carcinoma; RTK = receptor tyrosine kinase. Clinical Genitourinary Cancer 2017 15, e145-e150DOI: (10.1016/j.clgc.2016.05.019) Copyright © 2016 Elsevier Inc. Terms and Conditions