MP39-02 COMPARATIVE GENOMIC PROFILING OF MATCHED PRIMARY AND METASTATIC TUMORS IN RENAL CELL CARCINOMAстатья из журнала
Аннотация: You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2017MP39-02 COMPARATIVE GENOMIC PROFILING OF MATCHED PRIMARY AND METASTATIC TUMORS IN RENAL CELL CARCINOMA Maria Becerra, Ed Reznik, Daniel Tennenbaum, Mahyar Kashan, Mazyar Ghanaat, Jozefina Casuscelli, Brandon Manley, Almedina Redzematovic, Shawn Mendonca, Maria Arcila, Jonathan Coleman, Paul Russo, James Hsieh, and A. Ari Hakimi Maria BecerraMaria Becerra , Ed ReznikEd Reznik , Daniel TennenbaumDaniel Tennenbaum , Mahyar KashanMahyar Kashan , Mazyar GhanaatMazyar Ghanaat , Jozefina CasuscelliJozefina Casuscelli , Brandon ManleyBrandon Manley , Almedina RedzematovicAlmedina Redzematovic , Shawn MendoncaShawn Mendonca , Maria ArcilaMaria Arcila , Jonathan ColemanJonathan Coleman , Paul RussoPaul Russo , James HsiehJames Hsieh , and A. Ari HakimiA. Ari Hakimi View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1176AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Evaluation of genetic divergence among primary (P) and metastatic (M) tumors in renal cell carcinoma (RCC) is limited to small or unmatched P-M cohorts. We aim to better characterize somatic mutation (SM) disparities in a cohort of matched P-M tumors. METHODS We prospectively sequenced 47 clear cell RCC (ccRCC) and 12 non-clear cell RCC (nccRCC) P-M matched pairs using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a custom 410-gene (previously 341) next-generation sequencing assay. RESULTS We detected 527 SM, with a mean (SD) of 4.5 (3.13) per sample. Overall concordance rate (shared mutations/total mutations) was 49% (46% for ccRCC vs 78% for nccRCC). Private mutations in the P tumors were present in 32 (68%) and 3 (25%) of the ccRCC and nccRCC cohorts, respectively. Private mutations in the M tumors were present in 32 (68%) of the ccRCC and in 3 (25%) of nccRCC patients (Figure 1a). Strikingly, SETD2 mutations were private to the M or the P in 70% (16/23), and PTEN alterations were private to the M in 66% (4/6). There were no shared ROS1 mutations, and 83% (5/6) of these were private to the M. In a patient-by-patient analysis, 17% (10) of the pairs shared all SM; 15% (9) shared all of the SM in the M, with only private SM in the P; 25% (15) shared all SM in the P, with private SM only in the M; 42% (25) shared SM in the P-M; and some SM were private to either the P or the M. Only 14 pairs showed two SM in the same gene (Figure 1b); in 57% (8) the M presented a mutation in the same gene as the P but on a different location (convergent evolution), in 28% (4) the M presented both the mutation observed in the P and an additional mutation in the same gene (evolution of metastasis), and in 14% (2) the M showed a subclone of the SM observed in the P (sub-clonal seeding). CONCLUSIONS Our data suggest that both linear and parallel progression of metastases is observed in RCC. Although the absence of shared SM in matched pairs may be explained by tumor heterogeneity, metastasis-specific SM may represent cells of the P tumor with advantages to develop metastatic disease giving growth advantages in the studied samples. The extent to which the identified mutations contribute to the development of characteristics of metastatic spread needs to be analyzed further. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e493 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Maria Becerra More articles by this author Ed Reznik More articles by this author Daniel Tennenbaum More articles by this author Mahyar Kashan More articles by this author Mazyar Ghanaat More articles by this author Jozefina Casuscelli More articles by this author Brandon Manley More articles by this author Almedina Redzematovic More articles by this author Shawn Mendonca More articles by this author Maria Arcila More articles by this author Jonathan Coleman More articles by this author Paul Russo More articles by this author James Hsieh More articles by this author A. Ari Hakimi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Год издания: 2017
Авторы: Maria F. Becerra, Ed Reznik, Daniel M. Tennenbaum, Mahyar Kashan, Mazyar Ghanaat, Jozefina Casuscelli, Brandon J. Manley, Almedina Redzematovic, Shawn Mendonca, Maria E. Arcila, Jonathan Coleman, Paul Russo, James J. Hsieh, A. Ari Hakimi
Издательство: Lippincott Williams & Wilkins
Источник: The Journal of Urology
Ключевые слова: Renal cell carcinoma treatment, Renal and related cancers, Cancer Genomics and Diagnostics
Открытый доступ: bronze
Том: 197
Выпуск: 4S