ABCC2 p.Ala1119Thr
| Predicted by SNAP2: | C: N (61%), D: D (66%), E: D (59%), F: D (66%), G: N (82%), H: D (66%), I: N (53%), K: D (63%), L: D (59%), M: N (61%), N: N (61%), P: D (63%), Q: D (59%), R: D (66%), S: N (97%), T: N (93%), V: N (82%), W: D (75%), Y: D (59%), |
| Predicted by PROVEAN: | C: D, D: D, E: D, F: D, G: N, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: N, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Predictive factors of oxaliplatin neurotoxicity: t... Clin Cancer Res. 2007 Nov 1;13(21):6359-68. Gamelin L, Capitain O, Morel A, Dumont A, Traore S, Anne le B, Gilles S, Boisdron-Celle M, Gamelin E
Predictive factors of oxaliplatin neurotoxicity: the involvement of the oxalate outcome pathway.
Clin Cancer Res. 2007 Nov 1;13(21):6359-68., [PMID:17975148]
Abstract [show]
PURPOSE: Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites, oxalate, a calcium chelator. Different clinical approaches failed in neurotoxicity prevention, except calcium-magnesium infusions. We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids. We then looked for genetic predictive factors of oxaliplatin-induced neurotoxicity. EXPERIMENTAL DESIGN: We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion. In the second stage, before treatment with FOLFOX regimen, we prospectively looked for variants in genes coding for the enzymes involved (a) in the oxalate metabolism, especially glyoxylate aminotransferase (AGXT), and (b) in the detoxification glutathione cycle, glutathione S-transferase pi, and for genes coding for membrane efflux proteins (ABCC2). RESULTS: In the first 10 patients, urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion, accompanied by increased excretions of four amino acids (glycine, alanine, serine, and taurine) linked to oxalate metabolism. In a further 135 patients, a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity. Neither glutathione S-transferase pi nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity. CONCLUSION: These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXT genotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity.
Comments [show]
None has been submitted yet.
No. Sentence Comment
115 The variants of AGXT, GHPR, GSTk, and ABCC2 genes being looked for Variants Amino acids AGXT 154C>T 11Pr>Leu 155C del Codon 45 stop 156Cins Codon 167 stop Duplication 74 bp intron 1 576T>A 152Phe>Ile 588G>A 156Gly>Arg 630G>A 170Gly>Arg 640G>A 173Cys>Tyr 819C>T 233Arg>Cys 820G>A 233Arg>His 853T>C 244Ile>Thr 860G>A 246TrpStop A1119T Arg333Stop A1142G Ile340Met GRHPR 103Gdel (codon 35) 45LeuStop 295C>T 99ArgStop [AAGT]del Splicing error (codon 135 stop) 494G>A 165Gly>Asp G/A intron G Deletion of exon 8 965T>G Met322Arg GSTk 313A>G Ile105Val 341C/T Ala114Val ABCC2 24C>T 3972C>T Predictive Factors of Oxaliplatin Neurotoxicity www.aacrjournals.org Clin Cancer Res 2007;13(21) November 1, 20076361 Statistical analysis Frequencies of the different gene variants and the toxic side effects were measured and then compared.
X
ABCC2 p.Ala1119Thr 17975148:115:326
status: NEW257 Results of the detection of the variants of AGXT and GRHPR genes in 135 patients and frequency of AGXT minor haplotype Variant Amino acids No. patients Variant Amino acids No. patients GRHPR AGXT 103Gdel (codon 35) 45LeuStop 0 154C>T 11Pr>Leu 45 (30%) 155 C del Codon 45 stop 0 156Cins Codon 167 stop 0 295C>T 99ArgStop 0 Duplication 74 bp intron 1 46 (30%) [AAGT]del Splicing error 0 576T>A 152Phe>Ile 0 (codon 135 stop) 588G>A 156Gly>Arg 0 630G>A 170Gly>Arg 0 640G>A 173Cys>Tyr 0 494G>A 165Gly>Asp 0 819C>T 233Arg>Cys 0 820G>A 233Arg>His 0 853T>C 244Ile>Thr 0 860G>A 246TrpStop 0 G/A intron G Deletion exon 8 0 A1119T Arg333Stop 0 A1142G Ile340Met 44 (30%) 965T>G Met322Arg 0 154C>T 1142A> genotype No. patients % CC AA (major haplotype) 102 68.5 CC AG (H) 1 0.6 CT AA (H) 2 1.3 CT AG (H) 36 24.2 CT GG (H) 1 0.6 TT AG (M) 1 0.6 TT GG (M) 6 4 Minor haplotype 47 31.5 NOTE: The genotype of the duplication of intron 1 is in brackets.
X
ABCC2 p.Ala1119Thr 17975148:257:613
status: NEW