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

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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>


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