Difference between revisions of "O-6-methylguanine-DNA methyltransferase"

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'''O-6-methylguanine-DNA methyltransferase''' (MGMT) is a gene encoding for O6-alkylguanine DNA alkyltransferase which is required for genomic stability.
'''O-6-methylguanine-DNA methyltransferase''', abbreviated '''MGMT''', is a gene encoding for O6-alkylguanine DNA alkyltransferase which is required for genomic stability.
Because the product can antagonize the efficiacy of alkylating substances, the methylation state of the MGMT gene determines whether tumor cells in [[glioblastoma]] would be responsive to therapy with [[temozolomide]]. A methylated (ie silenced) MGMT promotor is therefore a predictive and prognostic biomarker.<ref>{{Cite journal  | last1 = Stupp | first1 = R. | last2 = Hegi | first2 = ME. | last3 = Mason | first3 = WP. | last4 = van den Bent | first4 = MJ. | last5 = Taphoorn | first5 = MJ. | last6 = Janzer | first6 = RC. | last7 = Ludwin | first7 = SK. | last8 = Allgeier | first8 = A. | last9 = Fisher | first9 = B. | title = Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. | journal = Lancet Oncol | volume = 10 | issue = 5 | pages = 459-66 | month = May | year = 2009 | doi = 10.1016/S1470-2045(09)70025-7 | PMID = 19269895 }}</ref>
Because the product can antagonize the efficiacy of alkylating substances, the methylation state of the MGMT gene determines whether tumor cells in [[glioblastoma]] would be responsive to therapy with [[temozolomide]]. A methylated (ie silenced) MGMT promotor is therefore a predictive and prognostic biomarker.<ref>{{Cite journal  | last1 = Stupp | first1 = R. | last2 = Hegi | first2 = ME. | last3 = Mason | first3 = WP. | last4 = van den Bent | first4 = MJ. | last5 = Taphoorn | first5 = MJ. | last6 = Janzer | first6 = RC. | last7 = Ludwin | first7 = SK. | last8 = Allgeier | first8 = A. | last9 = Fisher | first9 = B. | title = Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. | journal = Lancet Oncol | volume = 10 | issue = 5 | pages = 459-66 | month = May | year = 2009 | doi = 10.1016/S1470-2045(09)70025-7 | PMID = 19269895 }}</ref>


MGMT testing in neuropathology is usually performed by semi-quantitative methylation-specific PCR, pyrosequencing, methylation-specific multiplexed ligation probe amplification (MS-MLPA)or methylation profiling arrays. MGMT immunohistochemistry is not recommended.<ref>{{Cite journal  | last1 = Quillien | first1 = V. | last2 = Lavenu | first2 = A. | last3 = Ducray | first3 = F. | last4 = Joly | first4 = MO. | last5 = Chinot | first5 = O. | last6 = Fina | first6 = F. | last7 = Sanson | first7 = M. | last8 = Carpentier | first8 = C. | last9 = Karayan-Tapon | first9 = L. | title = Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial. | journal = Oncotarget | volume = 7 | issue = 38 | pages = 61916-61929 | month = 09 | year = 2016 | doi = 10.18632/oncotarget.11322 | PMID = 27542245 }}</ref><ref>{{Cite journal  | last1 = Trabelsi | first1 = S. | last2 = Mama | first2 = N. | last3 = Ladib | first3 = M. | last4 = Karmeni | first4 = N. | last5 = Haddaji Mastouri | first5 = M. | last6 = Chourabi | first6 = M. | last7 = Mokni | first7 = M. | last8 = Tlili | first8 = K. | last9 = Krifa | first9 = H. | title = MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry. | journal = Clin Transl Oncol | volume = 18 | issue = 4 | pages = 391-7 | month = Apr | year = 2016 | doi = 10.1007/s12094-015-1381-0 | PMID = 26289551 }}</ref>
MGMT testing in neuropathology is usually performed by semi-quantitative methylation-specific PCR, [[pyrosequencing]], methylation-specific multiplexed ligation probe amplification (MS-MLPA)or methylation profiling arrays. MGMT immunohistochemistry is not recommended.<ref>{{Cite journal  | last1 = Quillien | first1 = V. | last2 = Lavenu | first2 = A. | last3 = Ducray | first3 = F. | last4 = Joly | first4 = MO. | last5 = Chinot | first5 = O. | last6 = Fina | first6 = F. | last7 = Sanson | first7 = M. | last8 = Carpentier | first8 = C. | last9 = Karayan-Tapon | first9 = L. | title = Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial. | journal = Oncotarget | volume = 7 | issue = 38 | pages = 61916-61929 | month = 09 | year = 2016 | doi = 10.18632/oncotarget.11322 | PMID = 27542245 }}</ref><ref>{{Cite journal  | last1 = Trabelsi | first1 = S. | last2 = Mama | first2 = N. | last3 = Ladib | first3 = M. | last4 = Karmeni | first4 = N. | last5 = Haddaji Mastouri | first5 = M. | last6 = Chourabi | first6 = M. | last7 = Mokni | first7 = M. | last8 = Tlili | first8 = K. | last9 = Krifa | first9 = H. | title = MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry. | journal = Clin Transl Oncol | volume = 18 | issue = 4 | pages = 391-7 | month = Apr | year = 2016 | doi = 10.1007/s12094-015-1381-0 | PMID = 26289551 }}</ref>


==See also==
*[[Neuropathology]].
*[[Temozolomide]].
 
==References==
{{Reflist|1}}


[[Category:Neuropathology]]
[[Category:Neuropathology]]

Latest revision as of 11:30, 9 July 2018

O-6-methylguanine-DNA methyltransferase, abbreviated MGMT, is a gene encoding for O6-alkylguanine DNA alkyltransferase which is required for genomic stability. Because the product can antagonize the efficiacy of alkylating substances, the methylation state of the MGMT gene determines whether tumor cells in glioblastoma would be responsive to therapy with temozolomide. A methylated (ie silenced) MGMT promotor is therefore a predictive and prognostic biomarker.[1]

MGMT testing in neuropathology is usually performed by semi-quantitative methylation-specific PCR, pyrosequencing, methylation-specific multiplexed ligation probe amplification (MS-MLPA)or methylation profiling arrays. MGMT immunohistochemistry is not recommended.[2][3]

See also

References

  1. ↑ Stupp, R.; Hegi, ME.; Mason, WP.; van den Bent, MJ.; Taphoorn, MJ.; Janzer, RC.; Ludwin, SK.; Allgeier, A. et al. (May 2009). "Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.". Lancet Oncol 10 (5): 459-66. doi:10.1016/S1470-2045(09)70025-7. PMID 19269895.
  2. ↑ Quillien, V.; Lavenu, A.; Ducray, F.; Joly, MO.; Chinot, O.; Fina, F.; Sanson, M.; Carpentier, C. et al. (09 2016). "Validation of the high-performance of pyrosequencing for clinical MGMT testing on a cohort of glioblastoma patients from a prospective dedicated multicentric trial.". Oncotarget 7 (38): 61916-61929. doi:10.18632/oncotarget.11322. PMID 27542245.
  3. ↑ Trabelsi, S.; Mama, N.; Ladib, M.; Karmeni, N.; Haddaji Mastouri, M.; Chourabi, M.; Mokni, M.; Tlili, K. et al. (Apr 2016). "MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry.". Clin Transl Oncol 18 (4): 391-7. doi:10.1007/s12094-015-1381-0. PMID 26289551.
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