Abstract-Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n= 50), benign (n=20) and healthy (n=20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66% and 75% for angiogenin, 70% and 82.5% for clusterin and 46% and 80% for voided urine cytology. Combined sensitivity of angiogenin and clusterin with urine cytology increased from 82 to 88%.

Aim: This study aimed to sequence BRCA1 & BRCA2 genes to identify the frequency of the detected genetic mutations in the disease progression of colorectal cancer (CRC) and to estimate colorectal cancer risks in those BRCA mutation carriers. Material and methods: 140 biopsy samples were collected from Egyptian patients categorized into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=62) patients as well as subjects with chronic colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants at 500x were annotated against Cosmic, dbSNP, exac all, Polyphen2, Sift and Clinvar databases. Results: Analysis revealed that BRCA1 gene harbored 26, 19, 8 and 11 variants in the CRC, CP, IBD and control groups; respectively. Exon 10 was the most affected exon harbored 7 pathogenic variants in the CRC group. Two out of 7 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.1961delA (11%) & c.3214delC (16%). Moreover, 3 common begnin SNP variants were found to be related to ethnicity (c.3548A>G (58%), c.2612C>T (60%), c.4900A>G (69%). Moreover, BRCA2 gene harbored 48, 29, 24 and 18 variants in the CRC, CP, IBD and control groups respectively. Exon 2, 11, 23 were the most affected exons harbored 12 pathogenic variants in the CRC group. Four out of 12 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.3860delA (8%), c.5351delA (18%), c.9097delA (24%) & c.36delT (34%). Conclusion: Our data showed that BRCA1 & BRCA2 genes analyzed by Next-Generation Sequencing (NGS) identifies large number of pathogenic and begnin variants that are crucial for understanding CRC predisposition and early detection. Also, developing personalized therapies that efficiently target the individual CRC-specific mutations. Key words: Egyptian Colorectal cancer, BRCA1, BRCA2, pathogenic, begnin, Next Generation Sequencing Citation Format: Amira Salah El-Din Youssef, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, Mohamed El-Hadidi, Ali Kishk, ola sayed, Abdel-Rahman N. Zekri. Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3615.

Aim: This study aimed to sequence custom 96 genes of tumor suppressor genes and oncogenes frequently associated with colorectal cancer (CRC) to identify the frequency of the detected genetic mutations in the disease progression of CRC patients and to develop personalized therapy in those somatic mutation carriers. Material and methods: Biopsy samples were collected from Egyptian patients classified into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=60) patients as well as subjects with chronic non-specific colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants with an average coverage of 500x were annotated against Cosmic and dbSNP and Clinvar databases. Results: Analysis revealed that 52 genes harbor 128, 47 genes harbor 111, 40 genes harbor 71 and 39 genes harbor 66 somatic variants were detected in the CRC, CP, IBD and control groups; respectively. ARID1A (c.5548dupG (5%)), ATM (c.2572T>C (10%)), AXIN2 (c.1975C>T (5%)), FLCN (c.1285dupC (8%)), KRAS (c.35G>T (8%)), MSH6 (c.3261dupC (5%)), SLC9A9 (c.1765A>G (10%)), TP53 (c.1024C>T (5%)) were found to be the highly frequently detected pathogenic CRC specific variants. We also identified 29 genes harbor 43 common variants. The highly frequently common detected variants were ACVR2A (c.1310delA), ATM (c.5557G>A), BRCA1 (c.3548A>G, c.2612C>T), BRCA2 (c.1114A>C), IGF2 (c.677delG), KIT (c.1621A>C), MLH1 (c.655A>G), MLK4 (c.2223G>T, c.2182G>A), PIK3CA (c.1173A>G), PTPN12 (c.964G>A), RET (c.2071G>A), TP53 (c.121delG, c.215C>G) Conclusion: Our data showed that our Egyptian genetic makeup is different from other population. Also, the identified somatic mutations are crucial for understanding cancer predisposition and developing personalized therapies for the Egyptian colorectal cancer patients. Citation Format: Amira Salah El-Din Youssef, Ahmed Moustafa, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, ola sayed, Abdel-Rahman N. Zekri. Somatic mutation profiling of colorectal cancer by targeted next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3616.