Integrated Genomic Analysis of Primary Prostate Tumor Foci and Corresponding Lymph Node Metastases Identifies Mutations and Pathways Associated with Metastasis

• DOI: 10.20944/preprints202310.1586.v1
• Publication Date: 2023-10-25T05:56:36Z
• Authors: Carlos S. Moreno; Cynthia L. Winham; Mehrdad Alemozaffar; Emma R. Klein; Ismaheel O. Lawal; Olayinka A. Abiod...; Dattatraya Patil; Benjamin G. Barwick; Yijian Huang; David M. Schuster; Martin G. Sanda; Osunkoya O. Adeboye
• Keywords: Primary tumor; Chromoplexy

Prostate cancer is a highly heterogeneous disease, and mortality mainly due to metastases, but the initial steps of metastasis have not been well characterized. We performed integrative whole exome sequencing transcriptome analysis primary prostate tumor foci corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. present evidence that while there are some cases clonally independent foci, 87% descended common ancestor. demonstrate genes related oxidative phosphorylation upregulated LNM African-American relative White patients. further show mutations TP53, FLT4, EYA1, NCOR2, CSMD3, PCDH15 enriched metastases. These findings were validated meta-analysis 3,929 tumors 2,721 reveal pattern molecular alterations underlying pathology metastatic cancer. contain multiple subclones already foci. observed enrichment several including understudied such as find EYA1 CSMD3 associated with poor outcome