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1. Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Author

Jeon, Ah-Jung, Teo, Yue-Yang, Sekar, Karthik, Chong, Shay Lee, Wu, Lingyan, Chew, Sin-Chi, Chen, Jianbin, Kendarsari, Raden Indah, Lai, Hannah, Ling, Wen Huan, Kaya, Neslihan Arife, Lim, Jia Qi, Ramasamy, Adaikalavan, Oguz, Gokce, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng-Chung, Kam, Juinn Huar, Madhavan, Krishnakumar, Kow, Alfred, Ganpathi, Iyer Shridhar, Lim, Tony Kiat Hon, Leow, Wei-Qiang, Loong, Shihleone, Loh, Tracy Jiezhen, Wan, Wei Keat, Soon, Gwyneth Shook Ting, Pang, Yin Huei, Yoong, Boon Koon, Ong, Diana Bee-Lan, Lim, Jasmine, de Villa, Vanessa H., Cruz, Rouchelle D.dela, Chanwat, Rawisak, Thammasiri, Jidapa, Bonney, Glenn K., Goh, Brian K. P., Tucker-Kellogg, Greg, Foo, Roger Sik Yin, and Chow, Pierce K. H.

Published
2023
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5. Additional file 6 of Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Author

Jeon, Ah-Jung, Teo, Yue-Yang, Sekar, Karthik, Chong, Shay Lee, Wu, Lingyan, Chew, Sin-Chi, Chen, Jianbin, Kendarsari, Raden Indah, Lai, Hannah, Ling, Wen Huan, Kaya, Neslihan Arife, Lim, Jia Qi, Ramasamy, Adaikalavan, Oguz, Gokce, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng-Chung, Kam, Juinn Huar, Madhavan, Krishnakumar, Kow, Alfred, Ganpathi, Iyer Shridhar, Lim, Tony Kiat Hon, Leow, Wei-Qiang, Loong, Shihleone, Loh, Tracy Jiezhen, Wan, Wei Keat, Soon, Gwyneth Shook Ting, Pang, Yin Huei, Yoong, Boon Koon, Ong, Diana Bee-Lan, Lim, Jasmine, de Villa, Vanessa H., Cruz, Rouchelle D.dela, Chanwat, Rawisak, Thammasiri, Jidapa, Bonney, Glenn K., Goh, Brian K. P., Tucker-Kellogg, Greg, Foo, Roger Sik Yin, and Chow, Pierce K. H.

Abstract

Additional file 6: Supplementary Table S7. Top 20 REACTOME and CGP gene sets from GSEA of 328 NAP genes.

Published
2023
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6. Additional file 10 of Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Author

Jeon, Ah-Jung, Teo, Yue-Yang, Sekar, Karthik, Chong, Shay Lee, Wu, Lingyan, Chew, Sin-Chi, Chen, Jianbin, Kendarsari, Raden Indah, Lai, Hannah, Ling, Wen Huan, Kaya, Neslihan Arife, Lim, Jia Qi, Ramasamy, Adaikalavan, Oguz, Gokce, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng-Chung, Kam, Juinn Huar, Madhavan, Krishnakumar, Kow, Alfred, Ganpathi, Iyer Shridhar, Lim, Tony Kiat Hon, Leow, Wei-Qiang, Loong, Shihleone, Loh, Tracy Jiezhen, Wan, Wei Keat, Soon, Gwyneth Shook Ting, Pang, Yin Huei, Yoong, Boon Koon, Ong, Diana Bee-Lan, Lim, Jasmine, de Villa, Vanessa H., Cruz, Rouchelle D.dela, Chanwat, Rawisak, Thammasiri, Jidapa, Bonney, Glenn K., Goh, Brian K. P., Tucker-Kellogg, Greg, Foo, Roger Sik Yin, and Chow, Pierce K. H.

Abstract

Additional file 10: Fig. S2. A. GSEA results for up-regulated genes in tumour tissues from all-patients (AP) analysis. B: GSEA results for down-regulated genes in tumour tissues from AP analysis. Across both panels, top chart shows results including all the up-regulated genes from the AP analysis, while the bottom chart excludes the genes also detected in PP analyses.

Published
2023
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7. Additional file 8 of Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Author

Jeon, Ah-Jung, Teo, Yue-Yang, Sekar, Karthik, Chong, Shay Lee, Wu, Lingyan, Chew, Sin-Chi, Chen, Jianbin, Kendarsari, Raden Indah, Lai, Hannah, Ling, Wen Huan, Kaya, Neslihan Arife, Lim, Jia Qi, Ramasamy, Adaikalavan, Oguz, Gokce, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng-Chung, Kam, Juinn Huar, Madhavan, Krishnakumar, Kow, Alfred, Ganpathi, Iyer Shridhar, Lim, Tony Kiat Hon, Leow, Wei-Qiang, Loong, Shihleone, Loh, Tracy Jiezhen, Wan, Wei Keat, Soon, Gwyneth Shook Ting, Pang, Yin Huei, Yoong, Boon Koon, Ong, Diana Bee-Lan, Lim, Jasmine, de Villa, Vanessa H., Cruz, Rouchelle D.dela, Chanwat, Rawisak, Thammasiri, Jidapa, Bonney, Glenn K., Goh, Brian K. P., Tucker-Kellogg, Greg, Foo, Roger Sik Yin, and Chow, Pierce K. H.

Abstract

Additional file 8: Supplementary Table S10. Top 20 REACTOME gene sets from GSEA of down-regulated and up-regulated genes in PG1.

Published
2023
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8. Additional file 3 of Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Author

Jeon, Ah-Jung, Teo, Yue-Yang, Sekar, Karthik, Chong, Shay Lee, Wu, Lingyan, Chew, Sin-Chi, Chen, Jianbin, Kendarsari, Raden Indah, Lai, Hannah, Ling, Wen Huan, Kaya, Neslihan Arife, Lim, Jia Qi, Ramasamy, Adaikalavan, Oguz, Gokce, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng-Chung, Kam, Juinn Huar, Madhavan, Krishnakumar, Kow, Alfred, Ganpathi, Iyer Shridhar, Lim, Tony Kiat Hon, Leow, Wei-Qiang, Loong, Shihleone, Loh, Tracy Jiezhen, Wan, Wei Keat, Soon, Gwyneth Shook Ting, Pang, Yin Huei, Yoong, Boon Koon, Ong, Diana Bee-Lan, Lim, Jasmine, de Villa, Vanessa H., Cruz, Rouchelle D.dela, Chanwat, Rawisak, Thammasiri, Jidapa, Bonney, Glenn K., Goh, Brian K. P., Tucker-Kellogg, Greg, Foo, Roger Sik Yin, and Chow, Pierce K. H.

Abstract

Additional file 3: Supplementary Table S4. Top 20 gene sets from GSEA of up-regulated and down-regulated genes in all-patients analysis.

Published
2023
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9. Pathological complete response in an advance stage IIIB non‐small cell lung cancer secondary to neoadjuvant osimertinib targeted therapy: A case report and review of literature.

Author

Soo, Chun Ian, Ong, Diana Bee‐Lan, Chin, Ka Kiat, Sia, Leng Cheng, Munusamy, Vijayan, Ibrahim, Nur Husna, Loh, Thian Chee, Tan, Jiunn Liang, Poh, Mau Ern, Wong, Chee Kuan, Pang, Yong Kek, and Liam, Chong Kin

Subjects
*NON-small-cell lung carcinoma, *LITERATURE reviews, *OSIMERTINIB, *POSITRON emission tomography, *NEOADJUVANT chemotherapy
Abstract

Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non‐small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC. A 67‐year‐old woman had a left lower lobe lung mass measuring 5.0 × 5.1 × 7.0 cm with an enlarged subcarinal lymph node (LN) on her positron emission tomography scan. Following biopsy, a diagnosis of stage IIIB N2 (cT3N2M0) EGFR exon 19 deletion mutation‐positive lung adenocarcinoma was established. NTT using osimertinib 80 mg once daily was commenced. Subsequent re‐imaging at 3 months (ycT2bN2M0), 6 months (ycT1cN2M0) and 9 months showed tumour downstaging and resolution of the subcarinal LN (ycT1cN0M0). She underwent left lower lobectomy with systematic nodal dissection. All surgical specimens demonstrated no evidence of malignant cells (ypT0N0). Osimertinib could be the preferred NTT for potentially resectable NSCLC. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study

Author

Zhai, Weiwei, primary, Lai, Hannah, additional, Kaya, Neslihan Arife, additional, Chen, Jianbin, additional, Yang, Hechuan, additional, Lu, Bingxin, additional, Lim, Jia Qi, additional, Ma, Siming, additional, Chew, Sin Chi, additional, Chua, Khi Pin, additional, Alvarez, Jacob Josiah Santiago, additional, Chen, Pauline Jieqi, additional, Chang, Mei Mei, additional, Wu, Lingyan, additional, Goh, Brian K P, additional, Chung, Alexander Yaw-Fui, additional, Chan, Chung Yip, additional, Cheow, Peng Chung, additional, Lee, Ser Yee, additional, Kam, Juinn Huar, additional, Kow, Alfred Wei-Chieh, additional, Ganpathi, Iyer Shridhar, additional, Chanwat, Rawisak, additional, Thammasiri, Jidapa, additional, Yoong, Boon Koon, additional, Ong, Diana Bee-Lan, additional, de Villa, Vanessa H, additional, Dela Cruz, Rouchelle D, additional, Loh, Tracy Jiezhen, additional, Wan, Wei Keat, additional, Zeng, Zeng, additional, Skanderup, Anders Jacobsen, additional, Pang, Yin Huei, additional, Madhavan, Krishnakumar, additional, Lim, Tony Kiat-Hon, additional, Bonney, Glenn, additional, Leow, Wei Qiang, additional, Chew, Valerie, additional, Dan, Yock Young, additional, Tam, Wai Leong, additional, Toh, Han Chong, additional, Foo, Roger Sik-Yin, additional, and Chow, Pierce Kah-Hoe, additional

Published
2021
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12. Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

Author

Chai,Chee-Shee, Liam,Chong-Kin, Poh,Mau-Ern, Ong,Diana Bee-Lan, Pang,Yong-Kek, Cheah,Phaik-Leng, Ho,Gwo-Fuang, and Alip,Adlinda

Subjects
Cancer Management and Research, respiratory tract diseases
Abstract

Chee-Shee Chai,1 Chong-Kin Liam,2 Mau-Ern Poh,2 Diana Bee-Lan Ong,3 Yong-Kek Pang,2 Phaik-Leng Cheah,3 Gwo-Fuang Ho,4 Adlinda Alip4 1Department of Medicine, Faculty of Medicine and Health Science, University Malaysia Sarawak, Kota Samarahan, Sarawak, Malaysia; 2Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaCorrespondence: Mau-Ern PohDepartment of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, MalaysiaTel +60 3 7949 4422Fax +60 3 7955 2253Email ernestpoh@gmail.comBackground: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI).Methods: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.Results: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84– 6.25, p = 0.104).Conclusion: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.Keywords: non-small cell lung cancer, epidermal growth factor receptor, acquired T790M mutation, independent predictor, tyrosine kinase inhibitor

Published
2020

14. Right Parapharyngeal Cavernous Hemangioma, A Rare Entity: Case Report and Literature Review

Author

Rose, S. Emelda, Toong, Liew Yew, Ghauth, Sakina, and Ong, Diana Bee-Lan

Abstract

Cavernous hemangioma is a noncancerous vascular growth that arises from different parts of the head and neck region. However, parapharyngeal space contributes a very small percentage for its occurrence. We present a case of right parapharyngeal cavernous hemangioma, a very rare clinical presentation. This is a 57-year-old female presented with throat discomfort for 3 months. Examination finding showed a soft, diffuse, and non-pulsating mass over the right upper jugulodigastric region. A contrasted computed topographic scan revealed multiple calcifications in right parapharyngeal space. T2-weighted magnetic resonance imaging showed right parapharyngeal space mass with high signal and multiple phleboliths and dynamic angiogram unremarkable. Surgical resection done via transcervical approach and histopathological report revealed cavernous hemangioma with calcified thrombi. In conclusion, surgical intervention is the mainstay treatment and transcervical approach which is adopted in this case is the commonest approach used in surgical resection of cavernous hemangioma.

Published
2024
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15. Enterobius vermicularis Salpingitis Seen in the Setting of Ectopic Pregnancy in a Malaysian Patient

Author

Ngui, Romano, primary, Ravindran, Sarala, additional, Ong, Diana Bee Lan, additional, Chow, Tak Kuan, additional, Low, Kah Pin, additional, Nureena, Zaidi Syeda, additional, Rajoo, Yamuna, additional, Chin, Yuee Teng, additional, Amir, Amirah, additional, Ahmad, Arine Fadzlun, additional, Lim, Yvonne Ai Lian, additional, and Mahmud, Rohela, additional

Published
2014
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16. Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study

Author

Zhai, Weiwei, Lai, Hannah, Kaya, Neslihan Arife, Chen, Jianbin, Yang, Hechuan, Lu, Bingxin, Lim, Jia Qi, Ma, Siming, Chew, Sin Chi, Chua, Khi Pin, Alvarez, Jacob Josiah Santiago, Chen, Pauline Jieqi, Chang, Mei Mei, Wu, Lingyan, Goh, Brian K P, Chung, Alexander Yaw-Fui, Chan, Chung Yip, Cheow, Peng Chung, Lee, Ser Yee, Kam, Juinn Huar, Kow, Alfred Wei-Chieh, Ganpathi, Iyer Shridhar, Chanwat, Rawisak, Thammasiri, Jidapa, Yoong, Boon Koon, Ong, Diana Bee-Lan, de Villa, Vanessa H, Dela Cruz, Rouchelle D, Loh, Tracy Jiezhen, Wan, Wei Keat, Zeng, Zeng, Skanderup, Anders Jacobsen, Pang, Yin Huei, Madhavan, Krishnakumar, Lim, Tony Kiat-Hon, Bonney, Glenn, Leow, Wei Qiang, Chew, Valerie, Dan, Yock Young, Tam, Wai Leong, Toh, Han Chong, Foo, Roger Sik-Yin, and Chow, Pierce Kah-Hoe

Abstract

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.Using a prospective cohort for Hepatocellular Carcinoma (the PLANET study), this work revealed a dynamic landscape of phenotypic intra-tumor heterogeneity, providing several novel approaches for patient treatment and prognosis prediction.

Published
2022
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17. Enterobius vermicularisSalpingitis Seen in the Setting of Ectopic Pregnancy in a Malaysian Patient

Author

Ngui, Romano, Ravindran, Sarala, Ong, Diana Bee Lan, Chow, Tak Kuan, Low, Kah Pin, Nureena, Zaidi Syeda, Rajoo, Yamuna, Chin, Yuee Teng, Amir, Amirah, Ahmad, Arine Fadzlun, Lim, Yvonne Ai Lian, and Mahmud, Rohela

Abstract

ABSTRACTWe report a rare and unusual case of invasive Enterobius vermicularisinfection in a fallopian tube. The patient was a 23-year-old Malaysian woman who presented with suprapubic pain and vaginal bleeding. A clinical diagnosis of ruptured right ovarian ectopic pregnancy was made. She underwent a laparotomy with a right salpingo-oophorectomy. Histopathological examination of the right fallopian tube showed eggs and adult remnants of E. vermicularis, and the results were confirmed using PCR and DNA sequencing.

Published
2014
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18. Cervical bronchogenic cyst in a toddler.

Author

Ooi KM, Saniasiaya J, Kulasegarah J, and Ong DL

Subjects
Female, Humans, Child, Child, Preschool, Neck diagnostic imaging, Neck pathology, Magnetic Resonance Imaging, Diagnosis, Differential, Bronchogenic Cyst diagnostic imaging, Bronchogenic Cyst surgery, Branchioma diagnosis, Precancerous Conditions pathology, Uterine Cervical Neoplasms pathology
Abstract

Bronchogenic cyst is a congenital abnormality arising from the tracheobronchial system. Localisation of such cysts in the head and neck region is rare. We report a girl in her early childhood with a painless enlarging right lateral neck mass diagnosed with a branchial cleft cyst based on clinical and radiological MRI findings. An incidental finding of a cervical bronchogenic cyst was made on the final histopathological specimen. Although rare, bronchogenic cysts should be considered as differential diagnoses for paediatric patients' lateral and midline cervical masses., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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19. E-cadherin downregulation at the infiltrating tumour front is associated with histological grade and stage in colorectal carcinoma of Malaysians.

Author

Dass SD, Cheah PL, Ong DB, Teoh KH, and Looi LM

Subjects
Antigens, CD, Biopsy, Carcinoma secondary, Colorectal Neoplasms pathology, Down-Regulation, Humans, Immunohistochemistry, Malaysia, Neoplasm Grading, Neoplasm Invasiveness, Neoplasm Staging, Predictive Value of Tests, Biomarkers, Tumor analysis, Cadherins analysis, Carcinoma chemistry, Colorectal Neoplasms chemistry
Abstract

Loss of E-cadherin, a 120 kDA transmembrane glycoprotein responsible for cell-cell adhesion, is one of the hallmarks of epithelial-mesenchymal-transition (EMT). E-cadherin expression was immunohistochemically studied in 94 histopathologically re-confirmed colorectal carcinomas (CRC) using a monoclonal antibody to E-cadherin (Dako: Clone NCH-38) on a Ventana Benchmark XT automated system. Each case was assessed for E-cadherin immunopositivity at two separate locations viz the tumour centre (TC) as well as the infiltrating front (IF). Expression was semiquantitated for proportion of immunopositive malignant cells as 0 (negative), 1 (1-25% staining), 2 (26-50% staining), 3 (51-75% staining) and 4 (>75% staining) and staining intensity: 0 (negative), 1 (weak), 2 (moderate) and 3 (strong). The final histoscore of E-cadherin immunopositivity was arbitrarily computed as proportion of immunopositivity multiplied by staining intensity of the malignant cells. E-cadherin histoscores were significantly lower at the IF (4.5±2.5) compared with TC (10.7±2.4). Furthermore, the histoscores were significantly reduced at the IF of 49 TNM III+IV tumours (3.6±2.5) compared with 45 II+III CRC (5.4±2.2). Reduction of E-cadherin expression was also noted in the 23 high grade (TC=8.6±3.2; IF=2.6±2.3) compared with 71 low grade tumours (TC=11.4±1.5; IF=5.1±2.3). E-cadherin is downregulated at the infiltrating front of CRC, possibly marking for EMT at this location. The downregulation is further enhanced amongst late stage and high grade tumours compared with earlier stage and low grade tumours; findings which are similar to that noted in CRC of other populations.

Published
2015

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