NUR SABRINA BINTE SAPARI
Email Address
csinurs@nus.edu.sg
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Publication Technical reproducibility of single-nucleotide and size-based DNA biomarker assessment using DNA extracted from formalin-fixed, paraffin-embedded tissues(Elsevier, 2015) Zhang Shenli; Tan Bee Huat Iain; Nur Sabrina Bte Sapari; Grabsch H.I.; Okines A.; Smyth E.C.; Aoyama T.; Hewitt L.C.; Inam I.; Bottomley D.; Nankivell M.; Stenning S.P.; Cunningham D.; Wotherspoon A.; Tsuburaya A.; Yoshikawa T.; Soong Chuan Teck Richie; Tan Boon Ooi Patrick; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREPublication Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study(Wiley-Liss Inc., 2018) Heong V.; Syn N.L.; Lee X.W.; Sapari N.S.; Koh X.Q.; Adam Isa Z.F.; Sy Lim J.; Lim D.; Pang B.; Thian Y.L.; Ng L.K.; Wong A.L.; Soo R.A.; Yong W.P.; Chee C.E.; Lee S.-C., Goh B.-C.; Soong R.; Tan D.S.P.; PHARMACOLOGY; DIAGNOSTIC RADIOLOGY; MEDICINE; CANCER SCIENCE INSTITUTE OF SINGAPORE; DUKE-NUS MEDICAL SCHOOL; PATHOLOGYThe value of precision oncology initiatives in Asian contexts remains unresolved. Here, we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker-driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next-generation sequencing (NGS) and routine clinicopathological assays, such as immunohistochemistry, copy number analysis and in situ hybridization tests, were performed on tumor samples. Actionable biomarker results were used to identify eligibility for early-phase, biomarker-driven clinical trials. Overall, NGS was successful in 365 of 396 patients (92%), achieving a mean depth of 1,943× and coverage uniformity of 96%. The median turnaround time from sample receipt to return of genomic results was 26.0 days (IQR, 19.0–39.0 days). Reportable mutations were found in 300 of 365 patients (82%). Ninety-one percent of patients at study enrollment indicated consent to receive incidental findings and willingness to undergo genetic counseling if required. The most commonly mutated oncogenes included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%) and KIT (3%); while the most frequently mutated tumor suppressor genes included TP53 (40%), SMARCB1 (12%), APC (8%), PTEN (6%) and SMAD4 (5%). Among 23 patients enrolled in genotype-matched trials, median progression-free survival was 2.9 months (IQR, 1.5–4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1–68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting ≥ 8 weeks. © 2017 UICCPublication Statistical Process Control Charts for Monitoring Next-Generation Sequencing and Bioinformatics Turnaround in Precision Medicine Initiatives(Frontiers Media S.A., 2021-09-24) Jain, Sneha Rajiv; Sim, Wilson; Ng, Cheng Han; Chin, Yip Han; Lim, Wen Hui; Syn, Nicholas L.; Kamal, Nur Haidah Bte Ahmad; Gupta, Mehek; Heong, Valerie; Lee, Xiao Wen; Sapari, Nur Sabrina; Koh, Xue Qing; Isa, Zul Fazreen Adam; Ho, Lucius; O’Hara, Caitlin; Ulagapan, Arvindh; Gu, Shi Yu; Shroff, Kashyap; Weng, Rei Chern; Lim, Joey S. Y.; Lim, Diana; Pang, Brendan; Ng, Lai Kuan; Wong, Andrea; Soo, Ross Andrew; Yong, Wei Peng; Chee, Cheng Ean; Lee, Soo-Chin; Goh, Boon-Cher; Soong, Richie; Tan, David S. P.; MEDICINE; DUKE-NUS MEDICAL SCHOOL; PATHOLOGYPurpose: Precision oncology, such as next generation sequencing (NGS) molecular analysis and bioinformatics are used to guide targeted therapies. The laboratory turnaround time (TAT) is a key performance indicator of laboratory performance. This study aims to formally apply statistical process control (SPC) methods such as CUSUM and EWMA to a precision medicine programme to analyze the learning curves of NGS and bioinformatics processes. Patients and Methods: Trends in NGS and bioinformatics TAT were analyzed using simple regression models with TAT as the dependent variable and chronologically-ordered case number as the independent variable. The M-estimator “robust” regression and negative binomial regression were chosen to serve as sensitivity analyses to each other. Next, two popular statistical process control (SPC) approaches which are CUSUM and EWMA were utilized and the CUSUM log-likelihood ratio (LLR) charts were also generated. All statistical analyses were done in Stata version 16.0 (StataCorp), and nominal P < 0.05 was considered to be statistically significant. Results: A total of 365 patients underwent successful molecular profiling. Both the robust linear model and negative binomial model showed statistically significant reductions in TAT with accumulating experience. The EWMA and CUSUM charts of overall TAT largely corresponded except that the EWMA chart consistently decreased while the CUSUM analyses indicated improvement only after a nadir at the 82nd case. CUSUM analysis found that the bioinformatics team took a lower number of cases (54 cases) to overcome the learning curve compared to the NGS team (85 cases). Conclusion: As NGS and bioinformatics lead precision oncology into the forefront of cancer management, characterizing the TAT of NGS and bioinformatics processes improves the timeliness of data output by potentially spotlighting problems early for rectification, thereby improving care delivery. © Copyright © 2021 Jain, Sim, Ng, Chin, Lim, Syn, Kamal, Gupta, Heong, Lee, Sapari, Koh, Isa, Ho, O’Hara, Ulagapan, Gu, Shroff, Weng, Lim, Lim, Pang, Ng, Wong, Soo, Yong, Chee, Lee, Goh, Soong and Tan.Publication Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5’UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer(Ivyspring International Publisher, 2019) Yoshikawa, T.; Aoyama, T.; Sakamaki, K.; Oshima, T.; Lin, J.; Zhang, S.; Sapari, N.S.; Soong, R.; Tan, I.; Chan, X.B.; Bottomley, D.; Hewitt, L.C.; Arai, T.; Teh, B.T.; Epstein, D.; Ogata, T.; Kameda, Y.; Miyagi, Y.; Tsuburaya, A.; Morita, S.; Grabsch, H.I.; Tan, P.; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); CANCER SCIENCE INSTITUTE OF SINGAPORE; DUKE-NUS MEDICAL SCHOOL; PATHOLOGYPurpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3’UTR, and TS 5’UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5’UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5’UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series. © The author(s).Publication Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer(2016) Bhattacharya B.; Low S.H.H.; Chong M.L.; Chia D.; Koh K.X.; Sapari N.S.; Kaye S.; Hung H.; Benoukraf T.; Soong R.; DEAN'S OFFICE (MEDICINE); CANCER SCIENCE INSTITUTE OF SINGAPORE; PATHOLOGYHistorically, understanding of acquired resistance (AQR) to combination treatment has been based on knowledge of resistance to its component agents. To test whether an altered drug interaction could be an additional factor in AQR to combination treatment, models of AQR to combination and single agent MEK and PI3K inhibitor treatment were generated. Combination indices indicated combination treatment of PI3K and MEK inhibitors remained synergistic in cells with AQR to single agent but not combination AQR cells. Differences were also observed between the models in cellular phenotypes, pathway signaling and drug cross-resistance. Genomics implicated TGFB2-EDN1 overexpression as candidate determinants in models of AQR to combination treatment. Supplementation of endothelin in parental cells converted synergism to antagonism. Silencing of TGFB2 or EDN1 in cells with AQR conferred synergy between PI3K and MEK inhibitor. These results highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction.Publication Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib(BioMed Central Ltd., 2015) Wong A.L.A.; Lim J.S.J.; Sinha A.; Gopinathan A.; Lim R.; Tan C.-S.; Soh T.; Venkatesh S.; Titin C.; Sapari N.S.; Lee S.-C.; Yong W.-P.; Tan D.S.P.; Pang B.; Wang T.-T.; Zee Y.-K.; Soong R.; Trnkova Z.; Lathia C.; Thiery J.-P.; Wilhelm S.; Jeffers M.; Goh B.-C.; PHARMACOLOGY; DIAGNOSTIC RADIOLOGY; MEDICINE; CANCER SCIENCE INSTITUTE OF SINGAPORE; PATHOLOGY