DESIGN, SETTING AND PARTICIPANTS: We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.
OUTCOME MEASURES: The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.
RESULTS: Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.
CONCLUSIONS: The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.
METHODS: We evaluated the expression patterns of 11 candidate miRNAs using quantitative real-time PCR in whole blood (n = 10) and muscle biopsy samples (n = 9) of DM1 patients, and compared them to those of normal control samples (whole blood, n = 10; muscle, n = 9).
RESULTS: In DM1 whole blood, miRNA-133a, -29b, and -33a were significantly upregulated, whereas miRNA-1, -133a, and -29c were significantly downregulated in the skeletal muscles compared to controls.
CONCLUSIONS: Our findings align to those reported in other studies and point towards pathways that potentially contribute toward pathogenesis in DM1. However, the currently available data is not sufficient for these miRNAs to be made DM1-specific biomarkers because they seem to be common to many muscle pathologies. Hence, they lack specificity, but reinforce the need for further exploration of DM1 biomarkers.
METHODS:: A literature search was done for articles published between 2002 and 2017 on Medline electronic databases. Of 249 titles identified, 38 fulfilled the inclusion criteria, with 14 articles related to quantifiable imaging parameters (heterogeneity, vascularity, diffusion, cell density, infiltrations, perfusion, and metabolite changes) and 24 articles relevant to molecular biomarkers linked to imaging.
RESULTS:: Genes found to correlate with various imaging phenotypes were EGFR, MGMT, IDH1, VEGF, PDGF, TP53, and Ki-67. EGFR is the most studied gene related to imaging characteristics in the studies reviewed (41.7%), followed by MGMT (20.8%) and IDH1 (16.7%). A summary of the relationship amongst glioma morphology, gene expressions, imaging characteristics, prognosis and therapeutic response are presented.
CONCLUSION:: The use of radiogenomics can provide insights to understanding tumour biology and the underlying molecular pathways. Certain MRI characteristics that show strong correlations with EGFR, MGMT and IDH1 could be used as imaging biomarkers. Knowing the pathways involved in tumour progression and their associated imaging patterns may assist in diagnosis, prognosis and treatment management, while facilitating personalised medicine.
ADVANCES IN KNOWLEDGE:: Radiogenomics can offer clinicians better insight into diagnosis, prognosis, and prediction of therapeutic responses of glioma.