Affiliations: Research Laboratories, P.D. Hinduja National Hospital
& Medical Research Centre, Mumbai, India
Note: [] Corresponding author: Dr. T.F. Ashavaid, Consultant
Biochemist, Head, Dept. Laboratory Medicine, Jt. Director Research,
P.D.Hinduja National Hospital & Medical Research Centre, Veer Savarkar
Marg, Mahim, Mumbai, 400 016, India. Tel.: +91 22 24447935; Fax: +91 22
24442318/24447309; E-mail: dr_tashavaid@hindujahospital.com
Abstract: Introduction: Development of DNA-based tests for TPMT/DPD
polymorphisms can help clinicians and patients to make important decisions
about cancer treatment. Also, due to lack of Indian data, we aimed at the
development and validation of these tests in Indian patients. Materials and Methods: Molecular assays were used for identifying TPMT/DPD variations;
validated by DNA sequencing. Results: Molecular assays have been used for
screening TPMT*2, *3A, *3B, *3C alleles and IVS14+1(G→A) in DPD gene. A
patient, exhibiting neutropenia on 6-MP was observed to be G460A-homozygote,
while, two Acute Lymphoblastic Leukemia (ALL) patients with side-effects
exhibited wild-type alleles. Two patients showing 6-MP side-effects and
responding well to the same drug at later stage also carried wild-type alleles. Discussion: G460A homozygosity in a patient allowed clinicians to stop
6-MP treatment, improving patient's health status. Two ALL patients showing
side-effects were wild-type, indicating presence of unidentified rare
variations. Two patients with wild-type allele showed side-effects during 6-MP
treatment, but responded well to same drug at later stage, suggesting
side-effects to be attributable to multiple biological and environmental
processes. Absence of IVS14+1(G→A) in DPD gene will not exclude
possibility of another mutation. Conclusion: Molecular assays for
determining common TPMT/DPD variations, can provide accurate diagnosis and
efficient therapies in future clinical studies.
