title: TPMT and DPD polymorphisms: Efficient screening method for Indian patients considering taking Thiopurine and 5-FU drugs.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Molecular assays for determining common TPMT/DPD variations, can provide accurate diagnosis and efficient therapies in future clinical studies.
authors.affiliation: P.D. Hinduja National Hospital & Medical Research Centre, Mumbai, India. dr_tashavaid@hindujahospital.com
authors.forename: T F
authors.initials: TF
authors.lastname: Ashavaid
authors.forename: Rani
authors.initials: R
authors.lastname: Raghavan
authors.forename: Swarup
authors.initials: S
authors.lastname: Shah
authors.forename: Asha
authors.initials: A
authors.lastname: Kapadia
authors.forename: Sachin
authors.initials: S
authors.lastname: Almel
authors.forename: Devendra
authors.initials: D
authors.lastname: Desai
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001483:Base Sequence; D017931:DNA Primers; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007194:India; D015122:Mercaptopurine / Q000008:administration & dosage / Q000627:therapeutic use*; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D015122:Mercaptopurine; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D005472:Fluorouracil