Publications by authors named "May Al-Rashed"

5 Publications

  • Page 1 of 1

Methylation Profiling of Medulloblastoma in a Clinical Setting Permits Sub-classification and Reveals New Outcome Predictions.

Front Neurol 2020 20;11:167. Epub 2020 Mar 20.

Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

Medulloblastoma (MB) is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, but assessments in Saudi Arabian (SA)-MB cases are sparse. MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3), and Group 4 (G4) tumors. The WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signaling, whilst G3/G4 tumors show recurrent chromosomal alterations. Given that each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. Here, we performed the first assessment of MB-DNA methylation patterns in an SA cohort using archival biopsy material (FPPE = 49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3, and G4). Furthermore, methylation analysis was able to reclassify tumors that could not be sub-grouped through next-generation sequencing, highlighting its superior accuracy for MB molecular classifications. Independent assessments demonstrated known clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates, and a large number of tumor-associated deaths. Taking our results together, we demonstrate that DNA methylation profiling enables the robust sub-classification of four disease sub-groups in archival FFPE biopsy material from SA-MB patients. Moreover, we show that the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.00167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100767PMC
March 2020

Recent Advances in Meningioma Immunogenetics.

Front Oncol 2019 8;9:1472. Epub 2020 Jan 8.

Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

Meningiomas are relatively common, and typically benign intracranial tumors, which in many cases can be cured by surgical resection. However, less prevalent, high grade meningiomas, grow quickly, and recur frequently despite treatment, leading to poor patient outcomes. Across tumor grades, subjective guidelines for histological analysis can preclude accurate diagnosis, and an insufficient understanding of recurrence risk can cloud the choice of optimal treatment. Improved diagnostic and prognostic markers capable of discerning between the 15 heterogeneous WHO recognized meningioma subtypes are necessary to improve disease management and identify new targeted drug treatments. In this review, we show the advances in molecular profiling and immunophenotyping of meningiomas, which may lead to the development of new personalized therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.01472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960175PMC
January 2020

Correlation between serum trace elements and risk of preeclampsia: A case controlled study in Riyadh, Saudi Arabia.

Saudi J Biol Sci 2017 Sep 14;24(6):1142-1148. Epub 2015 Feb 14.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

Preeclampsia is a serious medical complication during pregnancy. In response to an increasing number of preeclamptic cases and scarcity of data concerning the interrelation between trace element levels and preeclampsia, we carried out a hospital based case-control study in Riyadh, Saudi Arabia to study the correlation between levels of serum trace elements and risk of preeclampsia. One hundred and twenty pregnant women were enrolled in this study and divided into three groups of 40 each-Control group, HR group (women at high risk of preeclampsia) and PET group (Preeclampsia group). Serum trace element levels were estimated by inductively coupled plasma optical emission spectrophotometer. The analysis found that mean values of Ca, Mg and Zn were 90.08 ± 6.38, 19.33 ± 3.32 and 1.30 ± 0.83 mg/L respectively in normotensive control and 77.85 ± 4.47, 15.44 ± 1.43 and 0.98 ± 0.63 mg/L respectively in the HR group. The mean values of Ca, Mg and Zn in the preeclamptic group were 70.37 ± 4.66, 13.58 ± 1.98 and 0.67 ± 0.59 mg/L, respectively. Interelement analysis reflected a negative correlation between Ca and Mg and between Mg and Zn whereas positive correlation between Ca and Zn in preeclamptic women. However the correlation was not statistically significant. In conclusion, our study suggests that decreased levels of these trace elements in serum may act as predisposing factors in pathogenesis of Preeclampsia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sjbs.2015.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562381PMC
September 2017

RP1 and retinitis pigmentosa: report of novel mutations and insight into mutational mechanism.

Br J Ophthalmol 2012 Jul 8;96(7):1018-22. Epub 2012 Feb 8.

UCL Institute of Ophthalmology, Department of Genetics, London, UK.

Background/aim: Retinitis pigmentosa (RP) is the commonest form of retinal dystrophy and is usually inherited as a monogenic trait but with remarkable genetic heterogeneity. RP1 is one of the earliest identified disease genes in RP with mutations in this gene known to act both recessively and dominantly although the mutational mechanism remains unclear. This study is part of our ongoing effort to characterise RP in Saudi Arabia at the molecular level.

Methods: Homozygosity mapping and candidate gene analysis.

Results: The authors have identified four novel mutations, all recessive, in a number of families with a typical RP phenotype.

Conclusion: The distribution of these novel and previously reported RP1 mutations makes it challenging to describe a unifying mutational mechanism for dominant versus recessive RP1-related RP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2011-301134DOI Listing
July 2012

Autozygome maps dispensable DNA and reveals potential selective bias against nullizygosity.

Genet Med 2012 May 5;14(5):515-9. Epub 2012 Jan 5.

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Purpose: Copy number variants are an important source of human genome diversity. The widespread distribution of hemizygous copy number variants in the DNA of healthy humans suggests that haploinsufficiency is largely tolerated. However, little is known about the extent to which corresponding nullizygosity (two-copy deletion) is similarly tolerated.

Methods: We analyzed a cohort of first cousin unions to enrich for shared parental hemizygous events and tested their Mendelian inheritance in offspring.

Results: Analysis of autozygous DNA blocks (autozygome) in the offspring not only proved an efficient method of mapping "dispensable" DNA but also revealed potential selective bias against the occurrence of nullizygous changes. This bias was not restricted to genic copy number variants and was not accounted for by a high rate of miscarriages.

Conclusions: The autozygome is an efficient way to map dispensable segments of DNA and may reveal selective bias against nullizygosity in healthy individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/gim.2011.28DOI Listing
May 2012