ABSTRACT
BACKGROUND: Tumor protein 53 (TP53) is a tumor-suppressor gene and plays an essential role in apoptosis, cell cycle arrest, genomic stability, and DNA repair. Although it is the most often mutated gene in human cancer, it has respectively low frequency in hematological malignancy but is significantly linked with complex karyotype, poor prognosis, and chemotherapeutic response. Nevertheless, the prevalence and prognostic role of TP53 mutations in hematological malignancy in Saudi patients are not well reported. We, therefore, aim to assess the frequency of TP53 mutations in hematological malignancies in Saudi Arabia. METHOD: 20 different hematological malignancy samples were tested using fluorescence in situ hybridization (FISH) technique for TP53 deletion detection and next-generation sequencing (NGS) targeted panel was applied on 10 samples for mutations identification specifically TP53 mutation. RESULTS: TP53 deletion was detected in 6 of 20 samples by FISH. Most of the 6 patients with TP53 deletion had acute lymphoblastic leukemia (ALL), and majority of them were child. NGS result revealed one heterozygous missense mutation in exon 5 of the TP53 gene (c. G9963A, p.H175R). CONCLUSION: To the best of our knowledge, the TP53 mutation is novel variant, and the first time we are reporting their association with myelodysplastic syndromic individual with complex karyotype. This study recommends further analysis of genomic mutations on bigger cohorts, utilizing high throughput technologies.
ABSTRACT
Lynch syndrome is inherited in an autosomal dominant mode. Lynch syndrome is caused by impairment of one or more of the various genes (most frequently MLH1 and MSH2) involved in mismatch repair. In this study, whole genome comparative genomic hybridization array (array CGH) based genomic analysis was performed on twelve Saudi Lynch syndrome patients. A total of 124 chromosomal alterations (structural loss) were identified at mean log2 ratio cut off value of ±0.25. We also found structural loss in 2p21-p16.3, 3p23-p14.2, 7p22.1 and 1p34.1-p33 regions. These findings were subsequently validated by real time quantitative PCR showing downregulation of MSH2, MSH6, EPCAM, MLH1, PMS2 and MUTYH genes. These findings shall help in establishing database for alterations in mismatch repair genes underlying Lynch syndrome in Saudi population as well as to determine the incidence ratio of these disorders. Guided counselling will subsequently lead to the prevention and eradication of Lynch Syndrome in the local population.
