Data from Identification of a Novel Pathogenic Germline KDR Variant in Melanoma

• DOI: 10.1158/1078-0432.c.6523320.v1
• Publication Date: 2023-04-01T06:41:36Z
• Authors: Ines P. Silva; Amel Salhi; Keith M. Giles; Matjaz Vogelsang; Sung W. Han; Naima Ismaili; Kevin P. Lui; Eric M. Robinson; Melissa A. Wilson; Richard L. Shapiro; Anna Pavlick; Judy Zhong; Tomas Kirchhoff; Iman Osman

<div>Abstract<p><b>Purpose:</b> The application of pan-cancer next-generation sequencing panels in the clinical setting has facilitated identification low frequency somatic mutations and testing new therapies solid tumors using "basket trial" scheme. However, little consideration been given to relevance nonsynonymous germline variants, which are likely be uncovered may relevant prognostication prediction treatment response.</p><p><b>Experimental Design:</b> We analyzed matched tumor normal DNA from 34 melanoma patients an Ion Torrent cancer-associated gene panel. elected study variant Q472H kinase insert domain receptor (KDR), was identified 35% both a pilot independent 1,223 patient cohort. Using patient-derived cell lines human samples, we assessed proliferation, invasion, VEGF levels, angiogenesis by analyzing microvessel density (MVD) anti-CD34 antibody.</p><p><b>Results:</b> Serum levels MVD were significantly higher versus KDR wild-type (WD) patients. Primary cultures derived melanomas harboring more proliferative invasive than wild type. Finally, VEGFR2 antibody, showed that cells sensitive targeted inhibition VEGFR2, effect not observed WT cells.</p><p><b>Conclusions:</b> Our data support integration analysis into personalized decision-making suggest with might benefit antiangiogenesis treatment. <i>Clin Cancer Res; 22(10); 2377–85. ©2015 AACR</i>.</p></div>