TP53 Gene Alterations including Codon 72 Polymorphism in Patients with Multiple Myeloma
Journal Title: Journal of Clinical and Diagnostic Research - Year 2018, Vol 12, Issue 2
Abstract
ABSTRACT Introduction: Multiple Myeloma (MM) is a cytogenetically heterogeneous haematologic malignancy characterised by uncontrolled proliferation of clonal plasma cells within the bone marrow. TP53 gene inactivation is considered as an independent prognostic marker and patients harbouring these mutations are usually resistant to standard therapy. Aim: To determine the frequency of TP53 gene mutations in exons 4 to 9 and the distribution of Arg72Pro polymorphism in exon 4 in newly diagnosed multiple myeloma patients. Materials and Methods: Mutation analysis of genomic DNA from unsorted bone marrow aspirates of 30 patients (10 showed TP53 deletion by interphase FISH) and from peripheral blood lymphocytes of 30 healthy control individuals was performed by direct sequencing of amplified products using self-designed primers. The codon 72 polymorphism was studied using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique in an additional 108 MM patients and 70 healthy controls. Results: TP53 gene alterations were recorded in six patients (20%) and three of them showed two or more changes. No alterations were observed in exons 5, 7 and 9 in myeloma patients. Four mutations in codons c.284C>T (exon 4), c.641A>G (exon 6), c.787A>G and c.808T>G (exon 8) and three intronic variants c.672+48G>A (intron 6), c.782+72C>T and c.782+92T>G (intron 7) were seen only in the patient group. The variants c.108G>A (exon 4), c.672+62A>G (intron 6) and c.993+12T>C (intron 9) were observed in both groups. Three patients died within six months of diagnosis. The genotype and allele frequencies for Arg72Pro polymorphism were similar in the patient and in the control groups. Conclusion: The presence of TP53 mutations denoted a poor prognosis while the TP53 Pro72Arg polymorphism is not associated with increased risk for MM.
Authors and Affiliations
Perumal Govindasamy, Charles Sharchil, Nithya Mohan, Prabu Pandurangan, Anil Tarigopula, Rama Mani, Chandra R Samuel
Keywords
Related Articles
- EP ID EP511741
- DOI 10.7860/JCDR/2018/34222.11170
- Views 96
- Downloads 0
Reversible Sinusoidal Obstruction Syndrome with Nodular Regenerative Hyperplasia Following OxaliplatinBased Chemotherapy
Abstract Sinusoidal Obstruction Syndrome (SOS) is a form of hepatic injury characterized by damage to small hepatic vessels resulting in occlusion of the terminal hepatic venules and hepatic sinusoids. Oxaliplatin has be...
Relationship of on Admission Hypocalcaemia and Illness Severity as Measured by APACHE-II and SOFA Score in Intensive Care Patients’
Introduction: Hypocalcaemia is very much prevalent in critically ill patients yet very less is known about its association with severity of illness. Acute Physiology and Chronic Health Evaluation (APACHE) and Sequential...
Effect of Pilates on Lower Limb Strength, Dynamic Balance, Agility and Coordination Skills in Aspiring State Level Badminton Players
ABSTRACT Introduction: Badminton, considered as one of the fastest racquet sports in the world requires excellent strength, dynamic balance, quick reflexes and coordination. Pilates is a form of training that focuses on...
Cerebro-Placental Ratio in Women with Hypertensive Disorders of Pregnancy: A Reliable Predictor of Neonatal Outcome
ABSTRACT Introduction: About 10 million women develop pre-eclampsia per year. Intra-Uterine Growth Restriction (IUGR) is a common complication of Hypertensive disorders of pregnancy, due to failure of normal placental in...
Prevalence of Intussusception after Rotavirus Vaccination: A Hospital Based Study from Odisha, India
ABSTRACT Introduction: Intussusception is a common cause of bowel obstruction in children and results in significant morbidity and mortality. Most recent evidence shows a slight increase in risk of intussusception after...