Single-Nucleotide Polymorphism (SNP) Analysis in the ABC Half-Transporter ABCG2 (MXR/BCRP/ABCP1)
| العنوان: | Single-Nucleotide Polymorphism (SNP) Analysis in the ABC Half-Transporter ABCG2 (MXR/BCRP/ABCP1) |
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| المؤلفون: | Kuniaki Morisaki, Lyn Mickley Huff, Robert W. Robey, Yasumasa Honjo, Michael Dean, Susan E. Bates, Jeffrey Hung |
| المصدر: | Cancer Biology & Therapy. 1:696-702 |
| بيانات النشر: | Informa UK Limited, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Nonsynonymous substitution, Heterozygote, Cancer Research, Single-nucleotide polymorphism, Biology, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Loss of heterozygosity, Exon, Genotype, Tumor Cells, Cultured, ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, RNA, Messenger, RNA, Neoplasm, Peptide sequence, In Situ Hybridization, Fluorescence, Pharmacology, Genetics, Exons, Blotting, Northern, Molecular biology, Introns, Neoplasm Proteins, SNP genotyping, Gene Expression Regulation, Neoplastic, Oncology, Drug Resistance, Neoplasm, Karyotyping, Molecular Medicine, ATP-Binding Cassette Transporters, SNP array |
| الوصف: | Variations in the amino acid sequence of ABC transporters have been shown to impact substrate specificity. We identified two acquired mutations in ABCG2, the ABC half-transporter overexpressed in mitoxantrone-resistant cell lines. These mutations confer differences in substrate specificity and suggest that naturally occurring variants could also affect substrate specificity. To search for the existence of single nucleotide polymorphisms (SNPs) in ABCG2, we sequenced 90 ethnically diverse DNAs from the Single Nucleotide Polymorphism Discovery Resource representing the spectrum of human genotypes. We identified 3 noncoding SNPs in the untranslated regions, 3 nonsynonymous and 2 synonymous SNPs in the coding region and 7 SNPs in the intron sequences adjacent to the sixteen ABCG2 exons. Nonsynonymous SNPs at nucleotide 238 (V12M; exon 2) and nucleotide 625 (Q141K; exon 5) showed a greater frequency of heterozygosity (22.2% and 10%) than the SNP at 2062 (D620N; exon 16). Heterozygous changes at nucleotide 238 are in linkage disequilibrium with an SNP observed 36 bases downstream from the end of exon 2. No polymorphism at amino acid 482 was identified to correspond to the R to G or R to T mutations previously found in two drug resistant cell lines. Among 23 drug resistant sublines for which sequence at position 482 was determined, no additional mutations were found. Heterozygosity at amino acid 12 allowed us to identify overexpression of a single allele in a subset of drug resistant cell lines, a feature that could be exploited clinically in evaluating the significance of ABCG2 expression in malignancy. We conclude that ABCG2 is well conserved and that described amino acid polymorphisms seem unlikely to alter transporter stability or function. |
| تدمد: | 1555-8576 1538-4047 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f91e92c45d9b4ec12c7ff6a1b12eca7 https://doi.org/10.4161/cbt.322 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5f91e92c45d9b4ec12c7ff6a1b12eca7 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15558576 15384047 |
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