Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence
Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS g...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Menzies, Georgina E. [verfasserIn] Prior, Ian A. [verfasserIn] Brancale, Andrea [verfasserIn] Reed, Simon H. [verfasserIn] Lewis, Paul D. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2021 |
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| Übergeordnetes Werk: |
Enthalten in: Chemistry central journal - London : BioMed Central, 2007, 15(2021), 1 vom: 14. Sept. |
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| Übergeordnetes Werk: |
volume:15 ; year:2021 ; number:1 ; day:14 ; month:09 |
| Links: |
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| DOI / URN: |
10.1186/s13065-021-00777-8 |
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SPR045076448 |
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| 520 | |a Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. | ||
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10.1186/s13065-021-00777-8 doi (DE-627)SPR045076448 (SPR)s13065-021-00777-8-e DE-627 ger DE-627 rakwb eng 540 570 ASE 540 ASE Menzies, Georgina E. verfasserin aut Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. Sequence context (dpeaa)DE-He213 Mutation rates (dpeaa)DE-He213 RAS genes (dpeaa)DE-He213 Molecular dynamics (dpeaa)DE-He213 DNA (dpeaa)DE-He213 Structural distortion (dpeaa)DE-He213 Benzo[a]pyrene diol epoxide (dpeaa)DE-He213 Prior, Ian A. verfasserin aut Brancale, Andrea verfasserin aut Reed, Simon H. verfasserin aut Lewis, Paul D. verfasserin aut Enthalten in Chemistry central journal London : BioMed Central, 2007 15(2021), 1 vom: 14. Sept. (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:15 year:2021 number:1 day:14 month:09 https://dx.doi.org/10.1186/s13065-021-00777-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_22 GBV_ILN_2003 GBV_ILN_2027 GBV_ILN_4305 AR 15 2021 1 14 09 |
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10.1186/s13065-021-00777-8 doi (DE-627)SPR045076448 (SPR)s13065-021-00777-8-e DE-627 ger DE-627 rakwb eng 540 570 ASE 540 ASE Menzies, Georgina E. verfasserin aut Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. Sequence context (dpeaa)DE-He213 Mutation rates (dpeaa)DE-He213 RAS genes (dpeaa)DE-He213 Molecular dynamics (dpeaa)DE-He213 DNA (dpeaa)DE-He213 Structural distortion (dpeaa)DE-He213 Benzo[a]pyrene diol epoxide (dpeaa)DE-He213 Prior, Ian A. verfasserin aut Brancale, Andrea verfasserin aut Reed, Simon H. verfasserin aut Lewis, Paul D. verfasserin aut Enthalten in Chemistry central journal London : BioMed Central, 2007 15(2021), 1 vom: 14. Sept. (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:15 year:2021 number:1 day:14 month:09 https://dx.doi.org/10.1186/s13065-021-00777-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_22 GBV_ILN_2003 GBV_ILN_2027 GBV_ILN_4305 AR 15 2021 1 14 09 |
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10.1186/s13065-021-00777-8 doi (DE-627)SPR045076448 (SPR)s13065-021-00777-8-e DE-627 ger DE-627 rakwb eng 540 570 ASE 540 ASE Menzies, Georgina E. verfasserin aut Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. Sequence context (dpeaa)DE-He213 Mutation rates (dpeaa)DE-He213 RAS genes (dpeaa)DE-He213 Molecular dynamics (dpeaa)DE-He213 DNA (dpeaa)DE-He213 Structural distortion (dpeaa)DE-He213 Benzo[a]pyrene diol epoxide (dpeaa)DE-He213 Prior, Ian A. verfasserin aut Brancale, Andrea verfasserin aut Reed, Simon H. verfasserin aut Lewis, Paul D. verfasserin aut Enthalten in Chemistry central journal London : BioMed Central, 2007 15(2021), 1 vom: 14. Sept. (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:15 year:2021 number:1 day:14 month:09 https://dx.doi.org/10.1186/s13065-021-00777-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_22 GBV_ILN_2003 GBV_ILN_2027 GBV_ILN_4305 AR 15 2021 1 14 09 |
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10.1186/s13065-021-00777-8 doi (DE-627)SPR045076448 (SPR)s13065-021-00777-8-e DE-627 ger DE-627 rakwb eng 540 570 ASE 540 ASE Menzies, Georgina E. verfasserin aut Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. Sequence context (dpeaa)DE-He213 Mutation rates (dpeaa)DE-He213 RAS genes (dpeaa)DE-He213 Molecular dynamics (dpeaa)DE-He213 DNA (dpeaa)DE-He213 Structural distortion (dpeaa)DE-He213 Benzo[a]pyrene diol epoxide (dpeaa)DE-He213 Prior, Ian A. verfasserin aut Brancale, Andrea verfasserin aut Reed, Simon H. verfasserin aut Lewis, Paul D. verfasserin aut Enthalten in Chemistry central journal London : BioMed Central, 2007 15(2021), 1 vom: 14. Sept. (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:15 year:2021 number:1 day:14 month:09 https://dx.doi.org/10.1186/s13065-021-00777-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_22 GBV_ILN_2003 GBV_ILN_2027 GBV_ILN_4305 AR 15 2021 1 14 09 |
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10.1186/s13065-021-00777-8 doi (DE-627)SPR045076448 (SPR)s13065-021-00777-8-e DE-627 ger DE-627 rakwb eng 540 570 ASE 540 ASE Menzies, Georgina E. verfasserin aut Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. Sequence context (dpeaa)DE-He213 Mutation rates (dpeaa)DE-He213 RAS genes (dpeaa)DE-He213 Molecular dynamics (dpeaa)DE-He213 DNA (dpeaa)DE-He213 Structural distortion (dpeaa)DE-He213 Benzo[a]pyrene diol epoxide (dpeaa)DE-He213 Prior, Ian A. verfasserin aut Brancale, Andrea verfasserin aut Reed, Simon H. verfasserin aut Lewis, Paul D. verfasserin aut Enthalten in Chemistry central journal London : BioMed Central, 2007 15(2021), 1 vom: 14. Sept. (DE-627)525475176 (DE-600)2272440-0 1752-153X nnns volume:15 year:2021 number:1 day:14 month:09 https://dx.doi.org/10.1186/s13065-021-00777-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_22 GBV_ILN_2003 GBV_ILN_2027 GBV_ILN_4305 AR 15 2021 1 14 09 |
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540 570 ASE 540 ASE Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence Sequence context (dpeaa)DE-He213 Mutation rates (dpeaa)DE-He213 RAS genes (dpeaa)DE-He213 Molecular dynamics (dpeaa)DE-He213 DNA (dpeaa)DE-He213 Structural distortion (dpeaa)DE-He213 Benzo[a]pyrene diol epoxide (dpeaa)DE-He213 |
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Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence |
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Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence |
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Menzies, Georgina E. |
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Menzies, Georgina E. Prior, Ian A. Brancale, Andrea Reed, Simon H. Lewis, Paul D. |
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carcinogen-induced dna structural distortion differences in the ras gene isoforms; the importance of local sequence |
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Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence |
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Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. © The Author(s) 2021 |
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Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. © The Author(s) 2021 |
| abstract_unstemmed |
Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14. Results Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts. Conclusions We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development. © The Author(s) 2021 |
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