دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Integrated Genomic Analysis of Primary Prostate Tumor Foci and Corresponding Lymph Node Metastases Identifies Mutations and Pathways Associated with Metastasis.
المؤلفون: Moreno CS; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.; Department of Biomedical Informatics, Emory University, Atlanta, GA 30322, USA., Winham CL; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA., Alemozaffar M; Department of Urology, Emory University, Atlanta, GA 30322, USA., Klein ER; Emory College of Arts and Sciences, Atlanta, GA 30322, USA., Lawal IO; Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA., Abiodun-Ojo OA; Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA., Patil D; Department of Urology, Emory University, Atlanta, GA 30322, USA., Barwick BG; Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA., Huang Y; Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA., Schuster DM; Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA., Sanda MG; Department of Urology, Emory University, Atlanta, GA 30322, USA., Osunkoya AO; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.; Department of Urology, Emory University, Atlanta, GA 30322, USA.
المصدر: Cancers [Cancers (Basel)] 2023 Nov 30; Vol. 15 (23). Date of Electronic Publication: 2023 Nov 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: Prostate cancer is a highly heterogeneous disease and mortality is mainly due to metastases but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that, while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53 , FLT4 , EYA1 , NCOR2 , CSMD3 , and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3929 primary tumors and 2721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1 , CSMD3 , FLT4 , NCOR2 , and PCDH15 and found that mutations in EYA1 and CSMD3 are associated with a poor outcome in prostate cancer.
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معلومات مُعتمدة: R21-CA256375 United States CA NCI NIH HHS; R21 CA256375 United States CA NCI NIH HHS; P30 CA138292 United States CA NCI NIH HHS; U01 CA113913 United States CA NCI NIH HHS; U01-CA113913 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: cancer genomics; metastasis; prostate cancer; tumor heterogeneity
تواريخ الأحداث: Date Created: 20231209 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10705102
DOI: 10.3390/cancers15235671
PMID: 38067373
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6694
DOI:10.3390/cancers15235671