- Email: [email protected]
MP23-01 WHOLE GENOME DEEP SEQUENCING DECOMPOSES THE GENOME EVOLUTION OF RENAL CELL CARCINOMAS
THE JOURNAL OF UROLOGYâ
e242
CONCLUSIONS: The top six new gene expression markers KIFC1, TRIB1, NUSAP1, PRC1, UBE2C and TFDP1 showed excellent sensitivity and reproducibility. Overall, we present a list of potential BC genetic markers possessing a high diagnostic value. Source of Funding: none
MP22-19 HIGH NEGATIVE PREDICTIVE VALUE OF A CYTOGENETICALLY NORMAL BARBOTAGE (CNB) FISH IN PREDICTING BLADDER CANCER NON-RECURRENCE Eric Andresen*, Daniel Lee, Michael O’Donnell, Iowa City, IA INTRODUCTION AND OBJECTIVES: Urovysion’s FISH analysis is used to monitor bladder cancer recurrence in patients with a history of non-muscle invasive bladder cancer (NMIBC). However, the efficiency and use of a cytogenetically normal FISH obtained by saline barbotage wash has not been previously studied. The purpose of the study is to investigate whether a CNB FISH can be used to predict continued tumor free follow-up for patients with a history of NMIBC. METHODS: A retrospective chart review identified a cohort of 241 consecutive patients who were diagnosed with NMIBC from 2002 to 2008. We reviewed all of the FISH samples obtained from these patients during their follow-up visits. 344 total FISH analyses were identified in the cohort that had 3-month post-analysis cystoscopy and cytology. Of those, 165 were cytogenetically normal. We also identified 177 CNB FISH analyses that were followed at 6 months by a cystoscopy/cytology. Only FISH samples that were reported as completely cytogenetically normal (0/50 abnormal cells per sample) were included. Tumor recurrence was defined as either high-grade cytology and/or presence of tumor found during cystoscopy. If tumor was present, the pathology was noted whenever possible. RESULTS: Of the 165 CNB FISH analyses with a corresponding 3-month follow-up, 96.36% remained recurrence free (159/ 165). All recurrences at 3 months were identified by cystoscopy. Pathology from these patients were Ta high-grade (HG) - (2/6), indeterminate (2/6), Ta low-grade (LG) - (1/6) and bladder adenocarcinoma (1/ 6). Of the 177 FISH analyses with a corresponding 6-month follow-up, 93.79% of the patients were recurrence free (166/177). Recurrences were identified by cystoscopy (8/11) and cytology (3/11). Pathology for these cystoscopic recurrences included TaHG (1/8), TaLG (6/8), and indeterminate (1/8). All visible tumors were described as “small papillary lesions”. The three high-grade cytologies were eventually found to be bladder CIS. CONCLUSIONS: Our data supports that a CNB FISH is highly predictive of tumor free status at both 3 and 6 months, missing primarily small, low-stage papillary recurrences. A CNB FISH analysis may have value as an adjunct to cystoscopy and cytology for monitoring bladder cancer. Source of Funding: none
MP22-20
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
METHODS: 305 consecutive patients < 40 years old referred to the Urology Department at Aberdeen Royal Infirmary between January 1999 and September 2007 were included. Data was prospectively collected and patients were investigated using upper tract imaging and flexible cystoscopy. The point of last follow-up (October 2010) was at least 3 years from the end of the study period (19992007). The results were independently analysed by 2 authors (OMA and BS). RESULTS: 110 were referred for NVH and 195 patients were referred for VH. Overall, in total 89.8% (274/305) patients had no pathology, 7.9% (24/305) had benign pathology, and 2.3% (7/305) had malignant pathology (Table). In patients with VH, none under 19 years old age group had any pathology. Two bladder tumour was seen in 20-29 year age group, 4 bladder tumour and 1 renal tumour was seen in the 30-39 year age group. While calculi were the most common cause of VH in the male group (4.7%), simple renal cysts were the more prevalent diagnosis in the women’s group (4.3%). In patients with NVH, 98.2% (108/110), had no pathology, one patient each had a urinary tract infection (UTI) and a simple renal cyst. There were no malignancies diagnosed in this group and both patients with benign pathology were in the 30-39 year old age group. CONCLUSIONS: Almost 90% of patients under the age of 40 years investigated for haematuria will have no pathology. Malignancy was diagnosed in 3.6% of patients with VH and in none of the patients with NVH. This is the first study to demonstrate outcomes of haematuria in patients <40 years emphasising the importance of tailoring investigations to the type of haematuria and patient age. Diagnosis No Pathology Benign Pathology: Calculus (renal/ureteric) Cystitis/UTI Hydronephrosis Renal Cyst Urethral Stricture/Bladder Neck Stenosis Malignant Pathology: Bladder Tumour Bladder Tumour Total (asterisk)
Patient number *274* *24* 8 4 2 5 5 *7* 6 1 *305*
Source of Funding: None
Kidney Cancer: Basic Research I Moderated Poster Sunday, May 18, 2014
8:00 AM-10:00 AM
MP23-01
HEMATURIA UNDER 40 YEARS: WHO NEEDS INVESTIGATIONS? LONG PROSPECTIVE LARGE-COHORT STUDY
WHOLE GENOME DEEP SEQUENCING DECOMPOSES THE GENOME EVOLUTION OF RENAL CELL CARCINOMAS
Said Mishriki*, Aberdeen, United Kingdom; Omar Aboumarzouk, Cardiff, United Kingdom; Bhaskar Somani, Southampton, United Kingdom
Song Wu*, Hongbin Mei, Shenzhen, China, People’s Republic of
INTRODUCTION AND OBJECTIVES: Haematuria in patients <40 years of age poses a management dilemma. Although investigations are always recommended, most studies include all age groups. The outcome of investigations in patients with visible haematuria (VH) and non-visible haematuria (NVH) in this important age group is unknown.
INTRODUCTION AND OBJECTIVES: The existence of distinct sub-populations of malignant cells within and between tumors of individual patients represents a major obstacle to the effective treatment and personalized therapy for renal cell carcinomas (RCCs). However, heterogeneous RCCs serve as the unique resources for studying human tumor progression because they are intermixtures of different tumor cell sub-clones.
THE JOURNAL OF UROLOGYâ
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
METHODS: We sequenced the whole genomes of the tumor and normal tissues from 60 RCC patients (T4N0M1) with well-docu or greater. mented clinical data to a mean depth of 30¡A RESULTS: From the whole genome data, we identified somatic mutations and copy number alterations that may serve as the markers for and (or) possibly drive cancer progression. RCCs display two classes of structural variation: monogenomic and polygenomic tumors. We further deep-sequenced the whole genomes of several and more. Our representative cases with polygenomic tumors to 120¡A studies identified the early genomic events that occur in the founder cells and shed light on the genome evolution of RCCs. By using the somatic mutations as the lineage markers, we traced the genetic record of the emergence of different sub-clones over time and found the genomic events that drive divergence of the founder cells into different subgroups. CONCLUSIONS: This study deciphers the fine genetic architecture of the RCC genomes and allows us to determine the extent of sub-clonal diversities within the bulk tumor mass of RCC, to build a polygenetic tree of the cancer to define when the divergence occurs, and to reveal what mutational processes are involved in the different stages of tumor evolution. Source of Funding: none
MP23-02 THE CLUSTERED MICRORNA-23B/27B FUNCTION AS TUMOR SUPPRESSORS AND USEFUL PROGNOSTIC MARKERS IN RENAL CELL CARCINOMA Tomoaki Ishihara*, Takeshi Chiyomaru, Satoru Inoguchi, Hideki Enokida, Kagoshima, Japan; Naohiko Seki, Chiba, Japan; Masayuki Nakagawa, Kagoshima, Japan INTRODUCTION AND OBJECTIVES: A growing body of evidence suggests that microRNAs (miRNAs) play an important role in cancer diagnosis and therapy. MicroRNA-23b (miR-23b) and miR-27b are closely located on chromosome 9q22.32, so called clustered miRNAs. MiR-23b/27b cluster is down-regulated in several human malignancies. Our recent miRNA expression signature of renal cell carcinoma (RCC) revealed that miR-23b and miR-27b expression were reduced in RCC, suggesting that miR-23b/27b cluster is a candidate tumor suppressor. The aim of this study is to investigate the functional significance of miR-23b/27b cluster, and to identify its target genes in RCC. METHODS: We evaluated miR-23b and miR-27b expressions in 27 RCC clinical specimens and 27 normal kidney tissues by stemloop RT-PCR. We analyzed their correlation with clinicopathological features. Furthermore, overall survival (OS) of 27 RCC patients was evaluated using the Kaplan-Meier method. We performed gain-offunction studies (cell migration and invasion assays) by mature miRNAs transfection into RCC cell lines (A498 and 786-O). To identify the targets potentially regulated by the miR-23b/27b cluster, we applied genome-wide gene expression analysis and in silico study. RESULTS: The expression of miR-23b and miR-27b was significantly reduced in the RCC specimens (respectively, P<0.0001 and P¼0.0002). MiR-23b and miR-27b expression level were significantly lower in recurrence group of patients compared to no-recurrence group (P¼0.0147 and P¼0.0313). MiR-23b and miR-27b expression level was significantly lower in high T stage (over pT3) compared to low T stage (under pT2) (P¼0.0257 and P¼0.0146). MiR-23b/27b expression level was significantly lower in high grade group compared to low grade group (P¼0.0019). Kaplan-Meier analysis showed that the low miR-23b/27b group had lower OS probability compared to the high miR23b/27b group (P¼0.0664). Significant inhibitions of cell migration and invasion were observed in the miR-23b and miR-27b transfectants. In silico analysis exhibited 22 putative target oncogenes of miR-23b/ 27b cluster.
e243
CONCLUSIONS: Our data indicated that miR-23b/27b cluster functioned as pivotal suppressor of cell migration and invasion in RCC and might be a prognostic cancer biomarker. Source of Funding: None
MP23-03 SPECIFIC MIRNA SIGNATURES CHARACTERIZE DIFFERENT METASTATIC SITES IN CLEAR CELL RENAL CELL CARCINOMA Joana Heinzelmann, Franziska Stolzenbach, Robert Schneeweiss, Homburg/Saar, Germany; Ulrike Wickmann, Jena, Germany; Sophie Baumgart, Homburg/Saar, Germany; Mieczyslaw Gajda, Jena, € ckle, Kerstin Junker*, Homburg/Saar, Germany Germany; Michael Sto INTRODUCTION AND OBJECTIVES: MiRNAs are regulators of gene expression in tumorigenesis and progression. To identify miRNAs associated with metastasis miRNA expression in distant metastases was compared to primary clear cell renal cell carcinoma (ccRCC). METHODS: Total RNA of 27 primary ccRCC samples and 25 distant metastases (lung, bone and brain) was isolated from formalinfixed paraffin-embedded (FFPE) samples Microarray analyses were performed for a global miRNA expression profiling. Results were validated by qPCR. For miRNA target identification a ccRCC cell line (786O) was transfected with miRNAs differently expressed in metastatic primary tumors and metastases. RESULTS: We identified 9 miRNAs (including miR-30c and miR-126) with a similar expression in metastatic primary ccRCC and distant metastases from different metastatic sites compared to nonmetastatic primary ccRCC. 11 miRNAs (including miR-10b and miR204) were differently expressed in distant metastases compared to primary ccRCC. Furthermore, each metastatic site is characterized by a specific miRNA signature. Results were verified on selected miRNAs using qPCR. In vitro studies identified potential miRNA targets and associated metastasis related pathways. CONCLUSIONS: These data suggest that miRNAs play an important role in metastatic processes of ccRCC. Furthermore, our results regarding different metastatic sites suggest two important statements: Specific miRNAs characterize distant metastases in general but miRNA expression is associated with specific conditions at different metastatic sites. Thus, the data presented in this study give the base for a better understanding of the involvement of miRNAs as regulators of metastasis which opens new possibilities for new targeted therapy options. Source of Funding: none
MP23-04 POST-GWAS FUNCTIONAL CHARACTERIZATION OF THE 12P11.23 RENAL CANCER SUSCEPTIBILITY LOCUS Pierre Bigot*, Lea Jessop, Mitchell Machiela, Timothy Myers, Nilabja Sikdar, Stephen Chanock, Bethesda, MD INTRODUCTION AND OBJECTIVES: In previous GWAS studies, 4 different loci were associated with renal cell carcinoma (RCC). Two common variants, rs718314 and rs1049380, were significant at the 12p11.23 locus. Interestingly, rs1049380 has been recently confirmed in a validation study of RCC susceptibility and rs718314 was identified as being associated with waist-hip ratio. The objective of the present study was to perform a functional analysis of the 12p11.23 region in relation to RCC risk. METHODS: We performed an imputation-analysis within 1 Mb of rs718314 with three different study populations from a previously published GWAS of RCC (4197 cases and 8527 controls). We examined the significantly associated variants for sequence overlap with potential regulatory sites by cross referencing them with the ENCODE
e242
CONCLUSIONS: The top six new gene expression markers KIFC1, TRIB1, NUSAP1, PRC1, UBE2C and TFDP1 showed excellent sensitivity and reproducibility. Overall, we present a list of potential BC genetic markers possessing a high diagnostic value. Source of Funding: none
MP22-19 HIGH NEGATIVE PREDICTIVE VALUE OF A CYTOGENETICALLY NORMAL BARBOTAGE (CNB) FISH IN PREDICTING BLADDER CANCER NON-RECURRENCE Eric Andresen*, Daniel Lee, Michael O’Donnell, Iowa City, IA INTRODUCTION AND OBJECTIVES: Urovysion’s FISH analysis is used to monitor bladder cancer recurrence in patients with a history of non-muscle invasive bladder cancer (NMIBC). However, the efficiency and use of a cytogenetically normal FISH obtained by saline barbotage wash has not been previously studied. The purpose of the study is to investigate whether a CNB FISH can be used to predict continued tumor free follow-up for patients with a history of NMIBC. METHODS: A retrospective chart review identified a cohort of 241 consecutive patients who were diagnosed with NMIBC from 2002 to 2008. We reviewed all of the FISH samples obtained from these patients during their follow-up visits. 344 total FISH analyses were identified in the cohort that had 3-month post-analysis cystoscopy and cytology. Of those, 165 were cytogenetically normal. We also identified 177 CNB FISH analyses that were followed at 6 months by a cystoscopy/cytology. Only FISH samples that were reported as completely cytogenetically normal (0/50 abnormal cells per sample) were included. Tumor recurrence was defined as either high-grade cytology and/or presence of tumor found during cystoscopy. If tumor was present, the pathology was noted whenever possible. RESULTS: Of the 165 CNB FISH analyses with a corresponding 3-month follow-up, 96.36% remained recurrence free (159/ 165). All recurrences at 3 months were identified by cystoscopy. Pathology from these patients were Ta high-grade (HG) - (2/6), indeterminate (2/6), Ta low-grade (LG) - (1/6) and bladder adenocarcinoma (1/ 6). Of the 177 FISH analyses with a corresponding 6-month follow-up, 93.79% of the patients were recurrence free (166/177). Recurrences were identified by cystoscopy (8/11) and cytology (3/11). Pathology for these cystoscopic recurrences included TaHG (1/8), TaLG (6/8), and indeterminate (1/8). All visible tumors were described as “small papillary lesions”. The three high-grade cytologies were eventually found to be bladder CIS. CONCLUSIONS: Our data supports that a CNB FISH is highly predictive of tumor free status at both 3 and 6 months, missing primarily small, low-stage papillary recurrences. A CNB FISH analysis may have value as an adjunct to cystoscopy and cytology for monitoring bladder cancer. Source of Funding: none
MP22-20
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
METHODS: 305 consecutive patients < 40 years old referred to the Urology Department at Aberdeen Royal Infirmary between January 1999 and September 2007 were included. Data was prospectively collected and patients were investigated using upper tract imaging and flexible cystoscopy. The point of last follow-up (October 2010) was at least 3 years from the end of the study period (19992007). The results were independently analysed by 2 authors (OMA and BS). RESULTS: 110 were referred for NVH and 195 patients were referred for VH. Overall, in total 89.8% (274/305) patients had no pathology, 7.9% (24/305) had benign pathology, and 2.3% (7/305) had malignant pathology (Table). In patients with VH, none under 19 years old age group had any pathology. Two bladder tumour was seen in 20-29 year age group, 4 bladder tumour and 1 renal tumour was seen in the 30-39 year age group. While calculi were the most common cause of VH in the male group (4.7%), simple renal cysts were the more prevalent diagnosis in the women’s group (4.3%). In patients with NVH, 98.2% (108/110), had no pathology, one patient each had a urinary tract infection (UTI) and a simple renal cyst. There were no malignancies diagnosed in this group and both patients with benign pathology were in the 30-39 year old age group. CONCLUSIONS: Almost 90% of patients under the age of 40 years investigated for haematuria will have no pathology. Malignancy was diagnosed in 3.6% of patients with VH and in none of the patients with NVH. This is the first study to demonstrate outcomes of haematuria in patients <40 years emphasising the importance of tailoring investigations to the type of haematuria and patient age. Diagnosis No Pathology Benign Pathology: Calculus (renal/ureteric) Cystitis/UTI Hydronephrosis Renal Cyst Urethral Stricture/Bladder Neck Stenosis Malignant Pathology: Bladder Tumour Bladder Tumour Total (asterisk)
Patient number *274* *24* 8 4 2 5 5 *7* 6 1 *305*
Source of Funding: None
Kidney Cancer: Basic Research I Moderated Poster Sunday, May 18, 2014
8:00 AM-10:00 AM
MP23-01
HEMATURIA UNDER 40 YEARS: WHO NEEDS INVESTIGATIONS? LONG PROSPECTIVE LARGE-COHORT STUDY
WHOLE GENOME DEEP SEQUENCING DECOMPOSES THE GENOME EVOLUTION OF RENAL CELL CARCINOMAS
Said Mishriki*, Aberdeen, United Kingdom; Omar Aboumarzouk, Cardiff, United Kingdom; Bhaskar Somani, Southampton, United Kingdom
Song Wu*, Hongbin Mei, Shenzhen, China, People’s Republic of
INTRODUCTION AND OBJECTIVES: Haematuria in patients <40 years of age poses a management dilemma. Although investigations are always recommended, most studies include all age groups. The outcome of investigations in patients with visible haematuria (VH) and non-visible haematuria (NVH) in this important age group is unknown.
INTRODUCTION AND OBJECTIVES: The existence of distinct sub-populations of malignant cells within and between tumors of individual patients represents a major obstacle to the effective treatment and personalized therapy for renal cell carcinomas (RCCs). However, heterogeneous RCCs serve as the unique resources for studying human tumor progression because they are intermixtures of different tumor cell sub-clones.
THE JOURNAL OF UROLOGYâ
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
METHODS: We sequenced the whole genomes of the tumor and normal tissues from 60 RCC patients (T4N0M1) with well-docu or greater. mented clinical data to a mean depth of 30¡A RESULTS: From the whole genome data, we identified somatic mutations and copy number alterations that may serve as the markers for and (or) possibly drive cancer progression. RCCs display two classes of structural variation: monogenomic and polygenomic tumors. We further deep-sequenced the whole genomes of several and more. Our representative cases with polygenomic tumors to 120¡A studies identified the early genomic events that occur in the founder cells and shed light on the genome evolution of RCCs. By using the somatic mutations as the lineage markers, we traced the genetic record of the emergence of different sub-clones over time and found the genomic events that drive divergence of the founder cells into different subgroups. CONCLUSIONS: This study deciphers the fine genetic architecture of the RCC genomes and allows us to determine the extent of sub-clonal diversities within the bulk tumor mass of RCC, to build a polygenetic tree of the cancer to define when the divergence occurs, and to reveal what mutational processes are involved in the different stages of tumor evolution. Source of Funding: none
MP23-02 THE CLUSTERED MICRORNA-23B/27B FUNCTION AS TUMOR SUPPRESSORS AND USEFUL PROGNOSTIC MARKERS IN RENAL CELL CARCINOMA Tomoaki Ishihara*, Takeshi Chiyomaru, Satoru Inoguchi, Hideki Enokida, Kagoshima, Japan; Naohiko Seki, Chiba, Japan; Masayuki Nakagawa, Kagoshima, Japan INTRODUCTION AND OBJECTIVES: A growing body of evidence suggests that microRNAs (miRNAs) play an important role in cancer diagnosis and therapy. MicroRNA-23b (miR-23b) and miR-27b are closely located on chromosome 9q22.32, so called clustered miRNAs. MiR-23b/27b cluster is down-regulated in several human malignancies. Our recent miRNA expression signature of renal cell carcinoma (RCC) revealed that miR-23b and miR-27b expression were reduced in RCC, suggesting that miR-23b/27b cluster is a candidate tumor suppressor. The aim of this study is to investigate the functional significance of miR-23b/27b cluster, and to identify its target genes in RCC. METHODS: We evaluated miR-23b and miR-27b expressions in 27 RCC clinical specimens and 27 normal kidney tissues by stemloop RT-PCR. We analyzed their correlation with clinicopathological features. Furthermore, overall survival (OS) of 27 RCC patients was evaluated using the Kaplan-Meier method. We performed gain-offunction studies (cell migration and invasion assays) by mature miRNAs transfection into RCC cell lines (A498 and 786-O). To identify the targets potentially regulated by the miR-23b/27b cluster, we applied genome-wide gene expression analysis and in silico study. RESULTS: The expression of miR-23b and miR-27b was significantly reduced in the RCC specimens (respectively, P<0.0001 and P¼0.0002). MiR-23b and miR-27b expression level were significantly lower in recurrence group of patients compared to no-recurrence group (P¼0.0147 and P¼0.0313). MiR-23b and miR-27b expression level was significantly lower in high T stage (over pT3) compared to low T stage (under pT2) (P¼0.0257 and P¼0.0146). MiR-23b/27b expression level was significantly lower in high grade group compared to low grade group (P¼0.0019). Kaplan-Meier analysis showed that the low miR-23b/27b group had lower OS probability compared to the high miR23b/27b group (P¼0.0664). Significant inhibitions of cell migration and invasion were observed in the miR-23b and miR-27b transfectants. In silico analysis exhibited 22 putative target oncogenes of miR-23b/ 27b cluster.
e243
CONCLUSIONS: Our data indicated that miR-23b/27b cluster functioned as pivotal suppressor of cell migration and invasion in RCC and might be a prognostic cancer biomarker. Source of Funding: None
MP23-03 SPECIFIC MIRNA SIGNATURES CHARACTERIZE DIFFERENT METASTATIC SITES IN CLEAR CELL RENAL CELL CARCINOMA Joana Heinzelmann, Franziska Stolzenbach, Robert Schneeweiss, Homburg/Saar, Germany; Ulrike Wickmann, Jena, Germany; Sophie Baumgart, Homburg/Saar, Germany; Mieczyslaw Gajda, Jena, € ckle, Kerstin Junker*, Homburg/Saar, Germany Germany; Michael Sto INTRODUCTION AND OBJECTIVES: MiRNAs are regulators of gene expression in tumorigenesis and progression. To identify miRNAs associated with metastasis miRNA expression in distant metastases was compared to primary clear cell renal cell carcinoma (ccRCC). METHODS: Total RNA of 27 primary ccRCC samples and 25 distant metastases (lung, bone and brain) was isolated from formalinfixed paraffin-embedded (FFPE) samples Microarray analyses were performed for a global miRNA expression profiling. Results were validated by qPCR. For miRNA target identification a ccRCC cell line (786O) was transfected with miRNAs differently expressed in metastatic primary tumors and metastases. RESULTS: We identified 9 miRNAs (including miR-30c and miR-126) with a similar expression in metastatic primary ccRCC and distant metastases from different metastatic sites compared to nonmetastatic primary ccRCC. 11 miRNAs (including miR-10b and miR204) were differently expressed in distant metastases compared to primary ccRCC. Furthermore, each metastatic site is characterized by a specific miRNA signature. Results were verified on selected miRNAs using qPCR. In vitro studies identified potential miRNA targets and associated metastasis related pathways. CONCLUSIONS: These data suggest that miRNAs play an important role in metastatic processes of ccRCC. Furthermore, our results regarding different metastatic sites suggest two important statements: Specific miRNAs characterize distant metastases in general but miRNA expression is associated with specific conditions at different metastatic sites. Thus, the data presented in this study give the base for a better understanding of the involvement of miRNAs as regulators of metastasis which opens new possibilities for new targeted therapy options. Source of Funding: none
MP23-04 POST-GWAS FUNCTIONAL CHARACTERIZATION OF THE 12P11.23 RENAL CANCER SUSCEPTIBILITY LOCUS Pierre Bigot*, Lea Jessop, Mitchell Machiela, Timothy Myers, Nilabja Sikdar, Stephen Chanock, Bethesda, MD INTRODUCTION AND OBJECTIVES: In previous GWAS studies, 4 different loci were associated with renal cell carcinoma (RCC). Two common variants, rs718314 and rs1049380, were significant at the 12p11.23 locus. Interestingly, rs1049380 has been recently confirmed in a validation study of RCC susceptibility and rs718314 was identified as being associated with waist-hip ratio. The objective of the present study was to perform a functional analysis of the 12p11.23 region in relation to RCC risk. METHODS: We performed an imputation-analysis within 1 Mb of rs718314 with three different study populations from a previously published GWAS of RCC (4197 cases and 8527 controls). We examined the significantly associated variants for sequence overlap with potential regulatory sites by cross referencing them with the ENCODE