Journal article
Temozolomide-induced severe myelosuppression: analysis of clinically associated polymorphisms in two patients
Anti-cancer drugs, Vol.22(1), pp.104-110
01/01/2011
DOI: 10.1097/CAD.0b013e3283407e9f
PMID: 20938339
Abstract
Genotyping of putative determinants of temozolomide (TMZ)-induced life-threatening bone marrow suppression was performed in two patients with glioma treated with adjuvant TMZ and radiation therapy. DNA was extracted from the patients' mononuclear cells and genotyping of O-methylguanine-DNA-methyltransferase (MGMT), multidrug resistance (MDR1; also known as ABCB1), NQO1, and GSTP1 genes and analysis for the epigenetic silencing of specific MGMT gene promoters were carried out to evaluate the possible genetic determinants of increased risk of severe TMZ-induced myelosuppression. Although both patients were heterozygous for all ABCB1 single nucleotide polymorphisms and for rs12917 and rs1803965 in the MGMT gene, patient 1 was heterozygous for rs1695 in GSTP1 and rs2308327 in the MGMT gene. This patient also exhibited GG genotype for the MGMT single nucleotide polymorphisms, rs2308321, which is noteworthy for its 0.7% frequency globally. Epigenetic silencing of MGMT gene was not detected in either patient. Two single nucleotide polymorphisms identified in patient 1 (missense I143V and K178R polymorphisms; rs2308321 and rs2308327, respectively) have recently been shown to correlate with an increased risk of severe TMZ-induced myelosuppression. The polymorphisms identified in patient 2 have not been associated with an increased risk of severe TMZ-induced myelosuppression. Genotyping analyses of larger patient populations administered TMZ are required to validate the genetic determinants of severe TMZ-induced myelosuppression.
Details
- Title: Subtitle
- Temozolomide-induced severe myelosuppression: analysis of clinically associated polymorphisms in two patients
- Creators
- Robert K Sylvester - Dakota State UniversityPreston Steen - Fargo VA Health Care SystemJohn M Tate - West Central InitiativeMinesh MehtaRyan J Petrich - Dakota State UniversityAlexander Berg - Dakota State UniversityJill Kolesar - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Anti-cancer drugs, Vol.22(1), pp.104-110
- DOI
- 10.1097/CAD.0b013e3283407e9f
- PMID
- 20938339
- ISSN
- 0959-4973
- eISSN
- 1473-5741
- Language
- English
- Date published
- 01/01/2011
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695797402771
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