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  1. Yip WK, Choo CW, Leong VC, Leong PP, Jabar MF, Seow HF
    APMIS, 2013 Oct;121(10):954-66.
    PMID: 23992303 DOI: 10.1111/apm.12152
    Molecular alterations in KRAS, BRAF, PIK3CA, and PTEN have been implicated in designing targeted therapy for colorectal cancer (CRC). The present study aimed to determine the status of these molecular alterations in Malaysian CRCs as such data are not available in the literature. We investigated the mutations of KRAS, BRAF, and PTEN, the gene amplification of PIK3CA, and the protein expression of PTEN and phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110α) by direct DNA sequencing, quantitative real-time PCR, and immunohistochemistry, respectively, in 49 CRC samples. The frequency of KRAS (codons 12, 13, and 61), BRAF (V600E), and PTEN mutations, and PIK3CA amplification was 25.0% (11/44), 2.3% (1/43), 0.0% (0/43), and 76.7% (33/43), respectively. Immunohistochemical staining demonstrated loss of PTEN protein in 54.5% (24/44) of CRCs and no significant difference in PI3K p110α expression between CRCs and the adjacent normal colonic mucosa (p = 0.380). PIK3CA amplification was not associated with PI3K p110α expression level, but associated with male cases (100% of male cases vs 56% of female cases harbored amplified PIK3CA, p = 0.002). PI3K p110α expression was significantly higher (p = 0.041) in poorly/moderately differentiated carcinoma compared with well-differentiated carcinoma. KRAS mutation, PIK3CA amplification, PTEN loss, and PI3K p110α expression did not correlate with Akt phosphorylation or Ki-67 expression. KRAS mutation, PIK3CA amplification, and PTEN loss were not mutually exclusive. This is the first report on CRC in Malaysia showing comparable frequency of KRAS mutation and PTEN loss, lower BRAF mutation rate, higher PIK3CA amplification frequency, and rare PTEN mutation, as compared with published reports.
    Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics*
  2. Abdullah MI, Junit SM, Ng KL, Jayapalan JJ, Karikalan B, Hashim OH
    Int J Med Sci, 2019;16(3):450-460.
    PMID: 30911279 DOI: 10.7150/ijms.29935
    Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all cancers of the thyroid. It is also one of the few cancers with a rapidly increasing incidence. PTC is usually contained within the thyroid gland and generally biologically indolent. Prognosis of the cancer is excellent, with less than 2% mortality at 5 years. However, more than 25% of patients with PTC developed a recurrence during a long term follow-up. The present article provides an updated condensed overview of PTC, which focuses mainly on the molecular alterations involved and recent biomarker investigations.
    Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics
  3. Mohamed Yusoff AA, Abd Radzak SM, Mohd Khair SZN, Abdullah JM
    Exp Oncol, 2021 06;43(2):159-167.
    PMID: 34190524
    BACKGROUND: To date, BRAF mutations in brain tumor patients have not been characterized in the Malaysian population. Based on the numerous reported studies, there are main mutations that exist in BRAF gene in various types of cancers. A missense mutation in codon 600 of the BRAF nuclear oncogene (BRAFV600E) is the most prevalent hotspot point mutation that has been identified in multiple human malignancies.

    AIM: We here aimed to find out the frequency of BRAFV600E mutation in a series of Malaysian patients with brain tumors and if any association exists between BRAFV600E mutation and clinicopathological features of patients.

    MATERIAL AND METHODS: Fresh frozen tumor tissue samples from 50 Malaysian brain tumor patients were analyzed for BRAFV600E mutational status, and its correlation with clinicopathological features (including age, gender, and tumor localization such as intra-axial: within the brain substance or extra-axial: outside the brain substance) was examined.

    RESULTS: The overall BRAFV600E mutation frequency was determined to be 22% (in 11 of 50 patients). BRAFV600E was significantly correlated with the tumor location group, which shows BRAFV600E was more frequent in the intra-axial tumor than the extra-axial tumor group. In this study, we also observed that male patients were slightly more susceptible to BRAFV600E mutation, and this mutation was predominant in patients of the age group 

    Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics*
  4. Soo R, Mery L, Bardot A, Kanesvaran R, Keong TC, Pongnikorn D, et al.
    ESMO Open, 2022 Oct;7(5):100560.
    PMID: 35988454 DOI: 10.1016/j.esmoop.2022.100560
    BACKGROUND: Lung cancer is the second most common cancer and leading cause of cancer mortality worldwide. Recent advances in molecular testing and targeted therapy have improved survival among patients with metastatic non-small-cell lung cancer (NSCLC). We sought to quantify and describe molecular testing among metastatic non-squamous NSCLC cases in selected Southeast Asian countries and describe first-line therapy chosen.

    PATIENTS AND METHODS: A retrospective study was conducted based on incident lung cancer cases diagnosed between 2017 and 2019 in Lampang (Thailand), Penang (Malaysia), Singapore and Yogyakarta (Indonesia). Cases (n = 3413) were defined using the International Classification of Diseases for Oncology third edition. In Singapore, a clinical series obtained from the National Cancer Centre was used to identify patients, while corresponding population-based cancer registries were used elsewhere. Tumor and clinical information were abstracted by chart review according to a predefined study protocol. Molecular testing of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangement, ROS1 gene rearrangement and BRAF V600 mutation was recorded.

    RESULTS: Among 2962 cases with a specified pathological diagnosis (86.8%), most patients had non-squamous NSCLC (75.8%). For cases with staging information (92.1%), the majority presented with metastatic disease (71.3%). Overall, molecular testing rates in the 1528 patients with stage IV non-squamous NSCLC were 67.0% for EGFR, 42.3% for ALK, 39.1% for ROS1, 7.8% for BRAF and 36.1% for PD-L1. Among these patients, first-line systemic treatment included chemotherapy (25.9%), targeted therapy (35.6%) and immunotherapy (5.9%), with 31% of patients having no record of antitumor treatment. Molecular testing and the proportion of patients receiving treatment were highly heterogenous between the regions.

    CONCLUSIONS: This first analysis of data from a clinically annotated registry for lung cancer from four settings in Southeast Asia has demonstrated the feasibility of integrating clinical data within population-based cancer registries. Our study results identify areas where further development could improve patient access to optimal treatment.

    Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics
  5. Ooi ZS, Pang SW, Teow SY
    Malays J Pathol, 2022 Dec;44(3):415-428.
    PMID: 36591710
    Colorectal cancer (CRC) remains among the most commonly diagnosed cancers and has been on the rise. It is also one of the most lethal diseases globally, being the third leading cause of cancerrelated death. Depending on the stages and disease conditions, CRC is treated by surgery, chemo-, radio-therapy, immunotherapy or in combination. However, these therapies have subpar results with unwanted side effects, hence continuous effort is ongoing to explore new type of therapeutic modalities. Among the sub-types of CRC, KRAS, BRAF and NRAS mutated CRC comprise approximately 43%, 10% and 3% of the total cases, respectively. These mutations are associated with tumour progression and anti-epidermal growth factor receptor (EGFR) treatment resistance. Due to their important role in CRC, these genes have thus become targets in the development of novel treatments. In this paper, we discuss the current and upcoming treatment on CRC by targeting these mutated genes, with more focus on KRAS and BRAF due to the higher occurrence of mutations in CRC.
    Matched MeSH terms: Proto-Oncogene Proteins B-raf/genetics
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