MP41-06 SPOP MUTATIONS IN PROSTATE CANCER ACROSS DEMOGRAPHICALLY DIVERSE PATIENT COHORTS. (2014)

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2014MP41-06 SPOP MUTATIONS IN PROSTATE CANCER ACROSS DEMOGRAPHICALLY DIVERSE PATIENT COHORTS. Mirjam Blattner, Daniel Lee, Catherine O'Reilly, Kyung Park, Theresa MacDonald, Francesca Khani, Kevin Turner, Ya-Lin Chiu, Peter Wild, Andrea Sboner, Sinan Ramazangolu, Haley Hieronymus, Charles Sawyers, Ashutosh Tewari, Ove Andren, Katja Fall, Francesca Demichelis, Juan Miguel Mosquera, Brian Robinson, Christopher Barbieri, and Mark Rubin Mirjam BlattnerMirjam Blattner More articles by this author , Daniel LeeDaniel Lee More articles by this author , Catherine O'ReillyCatherine O'Reilly More articles by this author , Kyung ParkKyung Park More articles by this author , Theresa MacDonaldTheresa MacDonald More articles by this author , Francesca KhaniFrancesca Khani More articles by this author , Kevin TurnerKevin Turner More articles by this author , Ya-Lin ChiuYa-Lin Chiu More articles by this author , Peter WildPeter Wild More articles by this author , Andrea SbonerAndrea Sboner More articles by this author , Sinan RamazangoluSinan Ramazangolu More articles by this author , Haley HieronymusHaley Hieronymus More articles by this author , Charles SawyersCharles Sawyers More articles by this author , Ashutosh TewariAshutosh Tewari More articles by this author , Ove AndrenOve Andren More articles by this author , Katja FallKatja Fall More articles by this author , Francesca DemichelisFrancesca Demichelis More articles by this author , Juan Miguel MosqueraJuan Miguel Mosquera More articles by this author , Brian RobinsonBrian Robinson More articles by this author , Christopher BarbieriChristopher Barbieri More articles by this author , and Mark RubinMark Rubin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1223AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene have been reported in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. Our objective was to investigate SPOP mutations across diverse cohorts, and validate a series of assays employing High Resolution Melting Analysis (HRM) and Sanger sequencing for mutational analysis of FFPE material. Methods 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both PSA-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, CHD1 deletion) as well as clinical and pathologic features. Fisher’s exact test and Chi-square analyses measured the differences in SPOP mutation rates and associations with molecular, clinical and pathologic features. Results Overall frequency of SPOP mutations was 8.1% in 720 samples (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (p<0.01), and SPOP mutant cancers had higher rates of CHD1 deletions (p<0.01). There were no significant differences in biochemical recurrence (BCR) in SPOP mutant cancers. Mutational assays showed excellent sensitivity and specificity in high quality samples. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. Conclusions SPOP is mutated in 4.6-14.4% of prostate cancer patients across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer. Further studies will be needed to establish the effect of mutant SPOP on clinical outcome. Molecular alterations by cohort Cohort No. of evaluable samples SPOP wt SPOP mutant ERG wt ERG positive PTEN wt PTEN deletion CHD1 wt CHD1 deletion African-American 88 84 (95.5%) 4 (4.5%) 66 (75.0%) 22 (25.0%) 78 (91.8%) 7 (8.2%) NA NA Korean 87 81 (93.1%) 6 (6.9%) 55 (70.5%) 23 (29.5%) 53 (82.8%) 11 (17.2%) NA NA Swedish 99 93 (93.9%) 6 (6.1%) 79 (79.8%) 20 (20.2%) NA NA 52 (82.5%) 11 (17.5%) Zurich 241 222 (92.1%) 19 (7.9%) 80 (45.5%) 96 (54.5%) 93 (51.7%) 87 (48.3%) NA NA MSKCC 80 75 (93.7%) 5 (6.3%) 38 (47.5%) 42 (52.5%) 75 (93.8%) 5 (6.2%) 67 (87.0%) 10 (13.0%) WCMC 125 107 (85.6%) 18 (14.4%) 65 (61.9%) 37 (35.2%) 82 (81.2%) 19 (18.8%) 36 (70.6%) 15 (29.4%) Demographic and molecular changes by SPOP mutation WT + SPOP P-value N (%) 662 / 720 (91.9%) 58 / 720 (8.1%) Median Age 65 (34-89) 64 (46-84) 0.49 Median PSA 7.1 7.4 0.65 Gleason Grade 0.26 6 97 (15.9%) 4 (7.3%) 3+4 230 (37.7%) 20 (36.4%) 4+3 132 (21.6%) 16 (29.1%) 8-10 151 (24.8%) 15 (27.3%) Pathological Stage 0.58 pT2 298 (62.6%) 29 (70.7%) pT3 166 (34.9%) 12 (29.3%) pT4 12 (2.5%) 0 Median Follow-up time, months (range) 73 (1.9-182) 100.5 (13-160) 0.67 Positive Biochemical Recurrence 70 (19.9%) 7 (25.9%) 0.45 Median time to BCR, months (range) 18 (1.2-139) 15 (11-55.4) 0.29 Status 0.69 NED 158 (50.8%) 10 (47.6%) AWD 65 (20.9%) 6 (28.6%) DOD 77 (24.8%) 4 (19.0%) DOC 11 (3.5%) 1 (4.8%) ERG < 0.01 WT 337 (59.4%) 46 (95.8%) Positive 230 (40.6%) 2 (4.2%) PTEN 0.31 WT 350 (74.1%) 31 (81.6%) Deletion 122 (25.9%) 7 (18.4%) CHD1 < 0.01 WT 147 (85.0%) 8 (42.1%) Deletion 26 (15.0%) 11 (57.9%) Key: BCR: biochemical recurrence; AWD: alive with disease; NED: no evidence of disease; DOD: died of disease; DOC: died of other causes; WT: wild-type © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e452-e453 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mirjam Blattner More articles by this author Daniel Lee More articles by this author Catherine O'Reilly More articles by this author Kyung Park More articles by this author Theresa MacDonald More articles by this author Francesca Khani More articles by this author Kevin Turner More articles by this author Ya-Lin Chiu More articles by this author Peter Wild More articles by this author Andrea Sboner More articles by this author Sinan Ramazangolu More articles by this author Haley Hieronymus More articles by this author Charles Sawyers More articles by this author Ashutosh Tewari More articles by this author Ove Andren More articles by this author Katja Fall More articles by this author Francesca Demichelis More articles by this author Juan Miguel Mosquera More articles by this author Brian Robinson More articles by this author Christopher Barbieri More articles by this author Mark Rubin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...