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Background Prostate cancer is one of the most commonly diagnosed cancers among men. African Americans (AA) are at an increased risk of developing prostate cancer compared to European Americans (EA). miRNAs play a critical role in these tumors, leading to tumor progression. In this study, we investigated the role of miR-182 in racial disparity in prostate cancer. Results We found significantly increased levels of miR-182 in prostate cancer tissues compared to BPH. Also, miR-182 shows increased expression in AA prostate cancer cell line and tissue samples compared to EA. We performed biochemical recurrence (BCR) - free survival time in AA and EA patients and found that high miR-182 expression had significantly shorter BCR-free survival than patients with low miR-182 expression (P = 0.031). To elucidate the role of miR-182, we knocked down miR-182 in EA (DU-145 and LNCaP) and AA (MDA-PCa-2b) cell lines and found an increase in apoptosis, arrest of the cell cycle, and inhibition of colony formation in the AA cell line to a greater extent than EA cell lines. Conclusions Our results showed that PDCD4 is a direct miR-182 target and its inhibition is associated with aggressiveness and high Gleason grade in prostate cancer among AA. These findings show that miR-182 is highly expressed in AA patients and miR-182 may be a target for effective therapy in AA patients.

Prostate carcinogenesis involves alterations in several signaling pathways, the most prominent being the PI3K/AKT pathway. This pathway is constitutively active and drives prostate cancer (PCa) progression to advanced metastatic disease. PTEN, a critical tumor and metastasis suppressor gene negatively regulates cell survival, proliferation, migration and angiogenesis via the PI3K/Akt pathway. PTEN is mutated, downregulated/dysfunctional in many cancers and its dysregulation correlates with poor prognosis in PCa. Here, we demonstrate that microRNA-4534 (miR-4534) is overexpressed in PCa and show that miR-4534 is hypermethylated in normal tissues and cell lines compared to PCa tissues/cells. miR-4534 exerts its oncogenic effects partly by downregulating the tumor suppressor PTEN gene. Knockdown of miR-4534 impaired cell proliferation, migration/invasion and induced G0/G1 cell cycle arrest and apoptosis in PCa. Suppression of miR-4534 and its effects on tumor growth was confirmed in a xenograft mouse model. We performed parallel experiments in non-cancer RWPE1 cells by overexpessing miR-4534 followed by functional assays. Overexpression of miR-4534 induced pro-cancerous characteristics in this non-cancer cell line. Statistical analyses revealed that miR-4534 has potential to independently distinguish malignant from normal tissues and positively correlated with poor overall and PSA recurrence free survival. Taken together, our results show that depletion of miR-4534 in PCa induces a tumor suppressor phenotype partly through induction of PTEN. These results have important implications for identifying and defining the role of new PTEN regulators such as microRNAs in prostate tumorigenesis. Understanding aberrantly overexpressed miR-4534 and its downregulation of PTEN will provide mechanistic insight and therapeutic targets for PCa therapy.

The incidence of prostate cancer (PCa) among African-Americans (AfA) is significantly higher than Caucasian-Americans (CaA) but the genetic basis for this disparity is not known. To address this problem, we analyzed miRNA expression in AfA (n = 81) and CaA (n = 51) PCa patients. Here, we found that miR-24 is differentially expressed in AfA and CaA PCa patients and attempt to clarify its role in AfA patients. Also, the public sequencing data of the miR-24 promoter confirmed that it was highly methylated and down-regulated in PCa patients. Utilizing a VAMCSF and NDRI patient cohorts, we discovered that miR-24 expression was linked to a racial difference between AfA/CaA PCa patients. Interestingly, miR-24 was restored after treatment of PCa cells with 5Aza-CdR in an AfA cell line (MDA-PCa-2b), while restoration of miR-24 was not observed in CaA cells, DU-145. Ectopic expression of miR-24 showed decreased growth and induced apoptosis, though the effect was less in the CaA cell line compared to the AfA cell line. Finally, we found unique changes in biological pathways and processes associated with miR-24 transfected AfA cells by quantitative PCR-based gene expression array. Evaluation of the altered pathways showed that AR, IGF1, IGFBP5 and ETV1 were markedly decreased in the AfA derived cell line compared with CaA cells, and there was a reciprocal regulatory relationship of miR-24/target expression in prostate cancer patients. These results demonstrate that miR-24 may be a central regulator of key events that contribute to race-related tumorigenesis and has potential to be a therapeutic agent for PCa treatment.

// Marisa Shiina 1, * , Yutaka Hashimoto 1, * , Taku Kato 1 , Soichiro Yamamura 1 , Yuichiro Tanaka 1 , Shahana Majid 1 , Sharanjot Saini 1 , Shahryari Varahram 1 , Priyanka Kulkarni 1 , Pritha Dasgupta 1 , Yozo Mitsui 1 , Mitsuho Sumida 1 , Laura Tabatabai 1 , Guoren Deng 1 , Deepak Kumar 2 , Rajvir Dahiya 1 1 Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA 2 Division of Science and Mathematic, Cancer Research Laboratory, University of the District of Columbia, Washington, DC, USA * These authors have contributed equally to this work Correspondence to: Rajvir Dahiya, email: rdahiya@ucsf.edu Keywords: miR-34b, prostate cancer, african-americans, caucasians, androgen receptor Received: October 04, 2016 Accepted: November 23, 2016 Published: December 25, 2016 ABSTRACT African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. miR-34b functions as a tumor suppressor and has a multi-functional role, through regulation of cell proliferation, cell cycle and apoptosis. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians. DNA hypermethylation of the miR-34b-3p promoter region showed significantly higher methylation in prostate cancer compared to normal samples. We then sequenced the promoter region of miR-34b-3p and found a chromosomal deletion in miR-34b in African-American prostate cancer cell line (MDA-PCA-2b) and not in Caucasian cell line (DU-145). We found that AR and ETV1 genes are differentially expressed in MDA-PCa-2b and DU-145 cells after overexpression of miR-34b. Direct interaction of miR-34b with the 3’ untranslated region of AR and ETV1 was validated by luciferase reporter assay. We found that miR-34b downregulation in African-Americans is inversely correlated with high AR levels that lead to increased cell proliferation. Overexpression of miR-34b in cell lines showed higher inhibition of cell proliferation, apoptosis and G1 arrest in the African-American cells (MDA-PCa-2b) compared to Caucasian cell line (DU-145). Taken together, our results show that differential expression of miR-34b and AR are associated with prostate cancer aggressiveness in African-Americans.

Purpose: Prostate cancer (PC) is the second most diagnosed cancer in men. African-American (AfA) men have higher incidence and twice the PC mortality rates compared to Caucasian-American (CaA) men. In this study, we investigated the biochemical role of miR-10a in prostate cancer racial disparity. Methods: We used PCa cell lines from CaA (DU145, LNCaP, PC3), AfA (MDA-PCa-2b, E006AA-hT) and a normal epithelial cell line (PWR1E) to examine miR-10a expression levels. Total RNA was extracted from total 138 human prostate cancer clinical samples (AfA: n=75, CaA: n=63) and cell lines. Gene expression levels were determined by quantitative real-time PCR (qPCR). A miRNA target database (miRWalk that integrates mainly three databases, miRDB, TargetScan and miRTarBase) was used for miR-10a target prediction. Cell proliferation and apoptosis were monitored after miR-10a knockdown by using anti-miR-10a. Results: miR-10a was significantly up-regulated in AfA prostate cancer cell line, E006AA-hT compared to CaA cells. Utilizing SFVAMC and NDRI patient cohorts, we confirmed that miR-10a expression was linked to a racial difference between AfA/CaA PCa patients. Knockdown of miR-10a showed decreased growth and apoptosis, though the effect was less in CaA compared to AfA cells. We found NCOR2 which is frequently deleted in castration- resistant prostate cancer patient specimens and tumor-suppressor PTEN as miR-10a targets that overlapped in multiple miRNA target prediction databases. Conclusion: These results demonstrate that miR-10a may be a central regulator of crucial events that contribute to racial differences in prostate cancer. Regulation of miR-10a expression may be a new therapeutic strategy for AfA prostate cancer patients. Citation Format: Yutaka Hashimoto, Marisa Shiina, Yuichiro Tanaka, Pritha Dasgupta, Priyanka Kulkarni, Taku Kato, Ryan K. Wong, Varahram Shahryari, Shigekatsu Maekawa, Soichiro Yamamura, Divya Bhagiratha, Sharanjot Saini, Guoren Deng, Laura Tabatabai, Shahana Majid, Rajvir Dahiya, Rajvir Dahiya. Up-regulation of miR-10a affect on prostate cancer racial disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 761.

Background: Renal cell carcinoma (RCC) is a leading cause of death, accounting for nearly 14,000 (~2.4%) deaths in the United States in 2017, with clear cell carcinoma (ccRCC) being the most common histologic subtype. New and precise disease progression biomarkers are needed for early detection and follow-up. Characterization of these new biomarkers offers a new approach for the identification of novel therapeutic targets and drugs for RCC treatment. MicroRNAs (miRNAs) act as either onco-miRs or tumor suppressors in cancer. Here we show a tumor-suppressor role for miR-182-5p in ccRCC and novel regulation of cell proliferation through MALAT-1. Methods: Profiling of miR-182-5p and MALAT-1 was performed in microdissected renal cancer tissues, matched adjacent normal regions and in human renal cancer cell lines by quantitative real-time PCR. To assess the functional significance of miR-182-5p in RCC, we overexpressed miR-182-5p/control miRNA (miR-CON) in RCC cell lines (ACHN, Caki-1) followed by functional assays. We also examined the therapeutic potential of synthetic miR-182-5p mimics in vivo using a renal cancer xenograft mouse model. We performed luciferase reporter assay and Ago2-RIP assay to investigate the interaction between miR-182-5p and MALAT-1. In addition, we assessed the effects of miR-182-5p overexpression and MALAT-1 downregulation on cell cycle progression in ccRCC cell lines. Results: Expression analyses in a cohort of renal cancer clinical specimens showed that miR-182-5p expression is frequently downregulated in ccRCC. We observed that overexpression of miR-182-5p inhibited cell proliferation, colony formation, apoptosis and led to G2/M arrest, supporting an antiproliferative role for this microRNA. Overexpression of miR-182-5p led to decreased expression of CDC20 and AURKA, drivers of the cell cycle mitotic phase. Also, overexpression of miR-182-5p directly lowered the expression of MALAT-1 and knockdown of MALAT-1 mimicked the effects of miR-182-5p overexpression. Downregulation of MALAT-1 led to upregulation of p53 that ultimately downregulated CDC20, AURKA. In vivo studies demonstrated that administration of miR-182-5p caused regression of established renal tumor xenografts. Conclusions: Collectively, these data suggest that miR-182-5p plays a tumor-suppressive role in ccRCC. These findings offer new insight into role of miR-182-5p in the inhibition of ccRCC tumor growth through MALAT-1 downregulation. This study may provide rationale for development of new strategies targeting MALAT-1 through miR-182-5p for treatment of ccRCC. Citation Format: Priyanka Kulkarni, Pritha Dasgupta, Shahana Majid, Varahram Shahryari, Marisa Shiina, Yutaka Hashimoto, Nadeem Bhat, Guoren Deng, Sharanjot Saini, Soichiro Yamamura, Yuichiro Tanaka, Rajvir Dahiya. miR-182-5p suppresses progression of renal cancer through cell cycle arrest by targeting lncRNA MALAT-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2478.

Background: MicroRNAs are small noncoding RNAs that regulate the expression of >60% of all human genes, either inhibiting target mRNA translation or inducing its degradation. MicroRNAs act as tumor suppressors or oncogenes in various cancers. The main objective of this study was to investigate the role of microRNA-588 (miR-588) in prostate cancer (PC). Methods: The methods employed in this study include quantitative-real time PCR; western blot; fluorescence-activated cell sorting assays for cell cycle distribution and apoptosis; assays for cell viability, migration and invasiveness of prostate cancer cells. Luciferase reporter assays and in-vivo study in nude mice was also performed. Results: The expression of miR-588 was significantly suppressed or silenced in PC tissue samples and cell lines when compared with normal tissues and a non-malignant cell line. Similar results were observed by analyzing the publicly available TCGA data sets for prostate adenocarcinoma. Functionally ectopic expression of miR-588 induced G0/G1 cell cycle arrest and apoptosis and suppressed cell proliferation. miR-588 exerted these functional effects by directly targeting the oncogenic Cyclin A2 that is involved in cancer cell cycle and proliferation. In silico algorithm showed a complimentary binding sequence in the 3'UTR of Cyclin A2 for miR-588. Over-expression of miR-588 significantly suppressed the luciferase activity of reporter plasmid containing the wild type 3'UTR sequences of cyclin A2 complementary to miR-588, which was abolished by mutations in these 3'UTR regions. miR-588 overexpression also significantly reduced the expression of cyclin A2 at both mRNA and protein levels. A significant decrease in the expression of various cell cycle pathway genes such as CycE1, MCM2, MCM4, CDC7 and CDT1 was also observed. These genes are involved in promoting cell cycle and proliferation and are overexpressed in prostate cancer. In vivo intracardiac implantation of PC3-MLuc-C6 prostate cancer cells constitutively expressing miR-588 showed a significant inhibition of the metastatic dissemination of these cells compared to the control miR expressing cells. Conclusion: This is the first study demonstrating that miR-588 is significantly silenced and acts as a tumor suppressor in prostate cancer. Reconstitution of silenced miR-588 may contribute to novel therapeutic approaches for regulating prostate cancer. Citation Format: Nadeem Bhat, Altaf A. Dar, Sharanjot Saini, Varahram Shahryari, Priyanka Kulkarni, Pritha Dasgupta, Soichiro Yamamura, Yuichiro Tanaka, Taku Kato, Yutaka Hashimoto, Marisa Shiina, Z. Laura Tabatabai, Guoren Deng, Rajvir Dahiya, Shahana Majid. Negative regulation of oncogenes by a novel tumor suppressor microRNA in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4292.

Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and polymorphic variants have been shown to increase activity levels. Lifestyle choices such as tobacco smoking and alcohol consumption are known to enhance the carcinogenesis process and in this study, how these factors may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population consisting of 405 healthy men and 400 prostate cancer patients were obtained. Of these, 507 were current or former smokers and 407 were alcohol drinkers. Eight polymorphic sites of the promoter region of CYP1B1 (rs2551188 G to A, rs2567206 G to A, rs2567207 A to G, rs162556 A to G, rs10175368 C to T, rs163090 T to A, rs162330 T to G, and rs162331 A to G) were analyzed in samples using Taqman genotyping assays and real-time PCR. Lifestyle factors and its influence on CYP1B1 polymorphisms toward cancer risks were also evaluated. Overall, both alcohol (P=0.006) and smoker (P=0.069) status were associated with prostate cancer. CYP1B1 variants were also risks for cancer at rs2551188 (P=0.043), rs2567206 (P=0.008), and rs10175368 (P=0.001). Evaluation of linkage disequilibrium show rs2551188, rs2567206, rs2567207, and rs10175368 to be linked and interestingly, the G-G-A-C haplotype (wildtype at respective sites) was significantly reduced in cancer (P=0.0282). When classified by lifestyle factors, no associations for CYP1B1 variants were found for cancer among non-smokers with rs10175368 (P=0.051) being a risk among non-drinkers. On the other hand, variants at both rs2567206 and rs10175368 showed increased cancer risk among smokers (P=0.032 and 0.002, respectively) as well as drinkers (P=0.044 and 0.019, respectively). No genotyping differences were observed when analyzing cancers by pathological grades. These results demonstrate smoker and alcoholic drinker status to modify the risks of CYP1B1 polymorphisms for prostate cancer and this is of importance in understanding their role in the pathogenesis of this disease. Citation Format: Taku Kato, Yutaka Hashimoto, Shigekatsu Maekawa, Marisa Shiina, Mitsuho Imai-Sumida, Pritha Dasgupta, Priyanka Kulkarni, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Varahram Sharryari, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Effects of tobacco smoking and alcohol consumption on risks of CYP1B1 polymorphisms for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2288. doi:10.1158/1538-7445.AM2017-2288

Loss of chromosome (chr) 8p21 is a frequent genomic alteration in prostate cancer (PCa). Genomic deletions of this region increase significantly with tumor grade and are associated with tumor progression and poor prognosis. A common region of loss of heterozygosity (LOH) has been mapped to the chr8p21 locus that primarily harbors prostate-specific NKX3.1 homeobox gene. We recently demonstrated that this frequently deleted locus is associated with a cluster of microRNA genes- miR-3622a/b- that are lost in prostate cancer and play an important mechanistic role in PCa progression and metastasis. MicroRNA expression profiling in microdissected human PCa clinical tissues showed that miR-3622a/b expression is widely downregulated and is correlated with poor survival outcome in prostate cancer. Our analyses suggested that miR-3622a has potential as a prognostic and diagnostic marker for prostate cancer. Extending these findings, we explored the prognostic potential of serum miR-3622a in prostate cancer patients. Since exosomes provide an important source of non-invasive, circulating biomarkers and represent an enriched source of microRNAs for biomarker profiling, we profiled the microRNA content of exosomes derived from sera of prostate cancer patients. In a pilot study, we profiled exosomal miRNAs from a training cohort of individuals with benign prostate hyperplasia (BPH), an indolent form of PCa or aggressive metastatic PCa. Exosomes were isolated from sera of prostate cancer patients and integrity of exosomal preparations was confirmed by nanoparticle tracking analysis and Western blot analyses for exosomal markers. Expression analyses of exosomal miR-3622a expression showed that this miRNA is enriched in exosomes. Higher levels of miR-3622a were significantly associated with tumor stage and lymph node metastasis in a cohort of prostate cancer clinical specimens. Further, ROC (Receiver Operating Characteristic) analyses showed that exosomal miR-3622a expression can be a single significant parameter to discriminate between BPH and prostate cancer. Overall, our data suggests that exosomal miR-3622a is a promising prognostic biomarker for prostate cancer. patients. Citation Format: Thao Yang, Divya Bhagirath, Kirandeep Sekhon, Nathan Bucay, Shahana Majid, Varahram Shahryari, Marisa Shiina, Yutaka Hashimoto, Priyanka Kulkarni, Pritha Dasgupta, Mitsuho Imai-Sumida, Soichiro Yamamura, Z Laura Tabatabai, Kirsten Greene, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng, Sharanjot Saini. Exosomal miR-3622a as prognostic marker in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4435. doi:10.1158/1538-7445.AM2017-4435

Prostate tumors are highly heterogeneous and molecular characterization based on biopsy sampling is often challenging. Hence, it is desirable to have an easily accessible, minimally invasive way to determine the molecular imprints of a patient’s tumor. Exosomes in blood are an important source of non-invasive, circulating biomarkers and provide an enriched source of microRNAs. With an objective of identifying microRNA based markers, we developed a comprehensive procedure for exosomal microRNA profiling analyses from sera of prostate cancer patients employing Nanostring nCounter technology. In a pilot study, we profiled exosomal miRNAs from a training cohort of normal individuals, patients with benign prostate hyperplasia (BPH), indolent form of PCa and aggressive metastatic prostate cancer. Exosomes were extracted from serum and the integrity of exosomal preparations was confirmed by nanoparticle tracking analysis and Western blot analyses for exosomal markers CD63, CD9 and TSG101. Levels of two miRNAs were significantly upregulated and several candidate miRNAs were markedly downregulated in metastatic PCa serum samples compared with controls. The candidate microRNAs were further validated in a larger cohort by real time PCR based microRNA assays. Of significance, we validated miR-1246 as an exosomal marker for prostate cancer. miR-1246 levels were specifically altered in prostate cancer patients and not significantly altered in BPH. Our analyses suggest that miR-1246 is a promising diagnostic biomarker for prostate cancer. Citation Format: Divya Bhagirath, Thao Yang, Kirandeep Sekhon, Nathan Bucay, Shahana Majid, Yutaka Hashimoto, Priyanka Kulkarni, Pritha Dasgupta, Marisa Shiina, Varahram Shahryari, Mitsuho Imai-Sumida, Soichiro Yamamura, Z Laura Tabatabai, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng, Sharanjot Saini. An exosomal biomarker for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5448. doi:10.1158/1538-7445.AM2017-5448

The incidence of prostate cancer (PCa) among African-Americans (AfA) is significantly higher than Caucasian-Americans (CaA) but the genetic basis for this disparity is not known. To address this problem, we analyzed miRNA expression in AfA (n=81) and CaA (n=51) PCa patients. Here, we found that miR-24 is differentially expressed in AfA and CaA PCa patients and attempt to clarify its role in AfA patients. Also, the public sequencing data of the miR-24 promoter confirmed that it was highly methylated and down-regulated in PCa patients. Utilizing a VAMCSF and NDRI patient cohorts, we discovered that miR-24 expression was linked to a racial difference between AfA/CaA PCa patients. Interestingly, miR-24 was restored after treatment of PCa cells with 5Aza-CdR in an AfA cell line (MDA-PCa-2b), while restoration of miR-24 was not observed in CaA cells, DU-145. Ectopic expression of miR-24 showed decreased growth and induced apoptosis, though the effect was less in the CaA cell line compared to the AfA cell line. Finally, we found unique changes in biological pathways and processes associated with miR-24 transfected AfA cells by quantitative PCR-based gene expression array. Evaluation of the altered pathways showed that AR, PDPK1, IGF1, and IGFBP5 were markedly decreased in the AfA derived cell line compared with CaA cells, and there was a reciprocal regulatory relationship of miR-24/target expression in prostate cancer patients. These results demonstrate that miR-24 may be a central regulator of key events that contribute to race-related tumorigenesis and has potential to be a therapeutic agent for PCa treatment. Citation Format: Yutaka Hashimoto, Marisa Shiina, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Varahram Shahryari, Priyanka Kulkarni, Pritha Dasgupta, Yozo Mitsui, Mitsuho Sumida, Guoren Deng, Laura Tabatabai, Deepak Kumar, Rajvir Dahiya. The role of miR-24 as a race-related genetic factor in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 462. doi:10.1158/1538-7445.AM2017-462

Aims and MethodTo examine the prevalence and admission patterns of patients with personality disorder admitted to a Scottish general adult psychiatry service. We carried out a retrospective case-note study of patients identified from the computerised patient administration system. A subgroup of patients was identified as having a longer in-patient stay. Their admission pattern over the preceding 4 years was studied further.ResultsSixty-two of 844 patients admitted had personality disorder. Thirty-nine had a primary diagnosis of personality disorder, 19 had an additional diagnosis of psychiatric disorder and 12 of alcohol or substance misuse. Within the subgroup admitted for longer in 2001, patterns of few/brief and numerous/often lengthy admissions were noted in earlier years.Clinical ImplicationsPersonality disorder occurs in approximately 7% of admissions to general adult psychiatry beds. Many have additional diagnoses of psychiatric disorder, or substance or alcohol misuse further complicating their treatment.