IDH mutation - Revision history

Jensflorian: /* General */ Update

2019-10-22T12:58:17Z

General: Update

← Older revision		Revision as of 12:58, 22 October 2019
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	Seen in:<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Reuss \| first2 = D. \| last3 = Schittenhelm \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = Bremer \| first5 = J. \| last6 = Sahm \| first6 = F. \| last7 = Harter \| first7 = PN. \| last8 = Jeibmann \| first8 = A. \| last9 = von Deimling \| first9 = A. \| title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. \| journal = Acta Neuropathol \| volume = 121 \| issue = 2 \| pages = 241-52 \| month = Feb \| year = 2011 \| doi = 10.1007/s00401-010-0770-2 \| PMID = 21069360 }}</ref>		Seen in:<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Reuss \| first2 = D. \| last3 = Schittenhelm \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = Bremer \| first5 = J. \| last6 = Sahm \| first6 = F. \| last7 = Harter \| first7 = PN. \| last8 = Jeibmann \| first8 = A. \| last9 = von Deimling \| first9 = A. \| title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. \| journal = Acta Neuropathol \| volume = 121 \| issue = 2 \| pages = 241-52 \| month = Feb \| year = 2011 \| doi = 10.1007/s00401-010-0770-2 \| PMID = 21069360 }}</ref>
	*Astrocytoma.		*Astrocytoma.
	*Oligodendroglioma (requirement for diagnosis).		*Oligodendroglioma (requirement for diagnosis).<ref>{{Cite journal \| last1 = Wesseling \| first1 = P. \| last2 = Capper \| first2 = D. \| title = WHO 2016 Classification of gliomas. \| journal = Neuropathol Appl Neurobiol \| volume = 44 \| issue = 2 \| pages = 139-150 \| month = 02 \| year = 2018 \| doi = 10.1111/nan.12432 \| PMID = 28815663 }}</ref>
	*Secondary Glioblastoma.		*Secondary Glioblastoma.
	**~~Ddx~~: IDH mutations in PNET are most likely misdiagnosed small cell glioblastomas.<ref>{{Cite journal \| last1 = Song \| first1 = X. \| last2 = Andrew Allen \| first2 = R. \| last3 = Terence Dunn \| first3 = S. \| last4 = Fung \| first4 = KM. \| last5 = Farmer \| first5 = P. \| last6 = Gandhi \| first6 = S. \| last7 = Ranjan \| first7 = T. \| last8 = Demopoulos \| first8 = A. \| last9 = Symons \| first9 = M. \| title = Glioblastoma with PNET-like components has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and likely a better prognosis than primary glioblastoma. \| journal = Int J Clin Exp Pathol \| volume = 4 \| issue = 7 \| pages = 651-60 \| month = \| year = 2011 \| doi = \| PMID = 22076165 }}</ref>		**DDx: IDH mutations in PNET are most likely misdiagnosed small cell glioblastomas.<ref>{{Cite journal \| last1 = Song \| first1 = X. \| last2 = Andrew Allen \| first2 = R. \| last3 = Terence Dunn \| first3 = S. \| last4 = Fung \| first4 = KM. \| last5 = Farmer \| first5 = P. \| last6 = Gandhi \| first6 = S. \| last7 = Ranjan \| first7 = T. \| last8 = Demopoulos \| first8 = A. \| last9 = Symons \| first9 = M. \| title = Glioblastoma with PNET-like components has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and likely a better prognosis than primary glioblastoma. \| journal = Int J Clin Exp Pathol \| volume = 4 \| issue = 7 \| pages = 651-60 \| month = \| year = 2011 \| doi = \| PMID = 22076165 }}</ref>

Jensflorian: /* General */ New entities added

2019-10-22T12:55:51Z

General: New entities added

← Older revision		Revision as of 12:55, 22 October 2019
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	*Oligodendroglioma (requirement for diagnosis).		*Oligodendroglioma (requirement for diagnosis).
	*Secondary Glioblastoma.		*Secondary Glioblastoma.
			**Ddx: IDH mutations in PNET are most likely misdiagnosed small cell glioblastomas.<ref>{{Cite journal \| last1 = Song \| first1 = X. \| last2 = Andrew Allen \| first2 = R. \| last3 = Terence Dunn \| first3 = S. \| last4 = Fung \| first4 = KM. \| last5 = Farmer \| first5 = P. \| last6 = Gandhi \| first6 = S. \| last7 = Ranjan \| first7 = T. \| last8 = Demopoulos \| first8 = A. \| last9 = Symons \| first9 = M. \| title = Glioblastoma with PNET-like components has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and likely a better prognosis than primary glioblastoma. \| journal = Int J Clin Exp Pathol \| volume = 4 \| issue = 7 \| pages = 651-60 \| month = \| year = 2011 \| doi = \| PMID = 22076165 }}</ref>



	Less common:		Less common:
	*Myeloproliferative disorders<ref>{{Cite journal \| last1 = Andrulis \| first1 = M. \| last2 = Capper \| first2 = D. \| last3 = Luft \| first3 = T. \| last4 = Hartmann \| first4 = C. \| last5 = Zentgraf \| first5 = H. \| last6 = von Deimling \| first6 = A. \| title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. \| journal = Leuk Res \| volume = 34 \| issue = 8 \| pages = 1091-3 \| month = Aug \| year = 2010 \| doi = 10.1016/j.leukres.2010.02.014 \| PMID = 20227112 }}</ref>		*Myeloproliferative disorders<ref>{{Cite journal \| last1 = Andrulis \| first1 = M. \| last2 = Capper \| first2 = D. \| last3 = Luft \| first3 = T. \| last4 = Hartmann \| first4 = C. \| last5 = Zentgraf \| first5 = H. \| last6 = von Deimling \| first6 = A. \| title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. \| journal = Leuk Res \| volume = 34 \| issue = 8 \| pages = 1091-3 \| month = Aug \| year = 2010 \| doi = 10.1016/j.leukres.2010.02.014 \| PMID = 20227112 }}</ref>
	*Cholangiocellular carcinoma<ref>{{Cite journal \| last1 = Zou \| first1 = S. \| last2 = Li \| first2 = J. \| last3 = Zhou \| first3 = H. \| last4 = Frech \| first4 = C. \| last5 = Jiang \| first5 = X. \| last6 = Chu \| first6 = JS. \| last7 = Zhao \| first7 = X. \| last8 = Li \| first8 = Y. \| last9 = Li \| first9 = Q. \| title = Mutational landscape of intrahepatic cholangiocarcinoma. \| journal = Nat Commun \| volume = 5 \| issue = \| pages = 5696 \| month = Dec \| year = 2014 \| doi = 10.1038/ncomms6696 \| PMID = 25526346 }}</ref>		*Cholangiocellular carcinoma<ref>{{Cite journal \| last1 = Zou \| first1 = S. \| last2 = Li \| first2 = J. \| last3 = Zhou \| first3 = H. \| last4 = Frech \| first4 = C. \| last5 = Jiang \| first5 = X. \| last6 = Chu \| first6 = JS. \| last7 = Zhao \| first7 = X. \| last8 = Li \| first8 = Y. \| last9 = Li \| first9 = Q. \| title = Mutational landscape of intrahepatic cholangiocarcinoma. \| journal = Nat Commun \| volume = 5 \| issue = \| pages = 5696 \| month = Dec \| year = 2014 \| doi = 10.1038/ncomms6696 \| PMID = 25526346 }}</ref><ref>{{Cite journal \| last1 = Farshidfar \| first1 = F. \| last2 = Zheng \| first2 = S. \| last3 = Gingras \| first3 = MC. \| last4 = Newton \| first4 = Y. \| last5 = Shih \| first5 = J. \| last6 = Robertson \| first6 = AG. \| last7 = Hinoue \| first7 = T. \| last8 = Hoadley \| first8 = KA. \| last9 = Gibb \| first9 = EA. \| title = Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. \| journal = Cell Rep \| volume = 18 \| issue = 11 \| pages = 2780-2794 \| month = 03 \| year = 2017 \| doi = 10.1016/j.celrep.2017.02.033 \| PMID = 28297679 }}</ref>
	*Esthesioneuroblastoma.<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Engel \| first2 = NW. \| last3 = Stichel \| first3 = D. \| last4 = Lechner \| first4 = M. \| last5 = Glöss \| first5 = S. \| last6 = Schmid \| first6 = S. \| last7 = Koelsche \| first7 = C. \| last8 = Schrimpf \| first8 = D. \| last9 = Niesen \| first9 = J. \| title = DNA methylation-based reclassification of olfactory neuroblastoma. \| journal = Acta Neuropathol \| volume = 136 \| issue = 2 \| pages = 255-271 \| month = 08 \| year = 2018 \| doi = 10.1007/s00401-018-1854-7 \| PMID = 29730775 }}</ref>		*Esthesioneuroblastoma.<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Engel \| first2 = NW. \| last3 = Stichel \| first3 = D. \| last4 = Lechner \| first4 = M. \| last5 = Glöss \| first5 = S. \| last6 = Schmid \| first6 = S. \| last7 = Koelsche \| first7 = C. \| last8 = Schrimpf \| first8 = D. \| last9 = Niesen \| first9 = J. \| title = DNA methylation-based reclassification of olfactory neuroblastoma. \| journal = Acta Neuropathol \| volume = 136 \| issue = 2 \| pages = 255-271 \| month = 08 \| year = 2018 \| doi = 10.1007/s00401-018-1854-7 \| PMID = 29730775 }}</ref>
			**DDx: Sinunasal undifferentiated carcinoma.<ref>{{Cite journal \| last1 = Dogan \| first1 = S. \| last2 = Chute \| first2 = DJ. \| last3 = Xu \| first3 = B. \| last4 = Ptashkin \| first4 = RN. \| last5 = Chandramohan \| first5 = R. \| last6 = Casanova-Murphy \| first6 = J. \| last7 = Nafa \| first7 = K. \| last8 = Bishop \| first8 = JA. \| last9 = Chiosea \| first9 = SI. \| title = Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. \| journal = J Pathol \| volume = 242 \| issue = 4 \| pages = 400-408 \| month = 08 \| year = 2017 \| doi = 10.1002/path.4915 \| PMID = 28493366 }}</ref>
			*Malignant melanoma.<ref>{{Cite journal \| last1 = Linos \| first1 = K. \| last2 = Tafe \| first2 = LJ. \| title = Isocitrate dehydrogenase 1 mutations in melanoma frequently co-occur with NRAS mutations. \| journal = Histopathology \| volume = 73 \| issue = 6 \| pages = 963-968 \| month = Dec \| year = 2018 \| doi = 10.1111/his.13707 \| PMID = 30003571 }}</ref>

	===Molecular background===		===Molecular background===

Jensflorian: /* General */

2019-10-22T06:36:47Z

General

← Older revision		Revision as of 06:36, 22 October 2019
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	==General==		==General==
	Seen in:<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Reuss \| first2 = D. \| last3 = Schittenhelm \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = Bremer \| first5 = J. \| last6 = Sahm \| first6 = F. \| last7 = Harter \| first7 = PN. \| last8 = Jeibmann \| first8 = A. \| last9 = von Deimling \| first9 = A. \| title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. \| journal = Acta Neuropathol \| volume = 121 \| issue = 2 \| pages = 241-52 \| month = Feb \| year = 2011 \| doi = 10.1007/s00401-010-0770-2 \| PMID = 21069360 }}</ref>		Seen in:<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Reuss \| first2 = D. \| last3 = Schittenhelm \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = Bremer \| first5 = J. \| last6 = Sahm \| first6 = F. \| last7 = Harter \| first7 = PN. \| last8 = Jeibmann \| first8 = A. \| last9 = von Deimling \| first9 = A. \| title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. \| journal = Acta Neuropathol \| volume = 121 \| issue = 2 \| pages = 241-52 \| month = Feb \| year = 2011 \| doi = 10.1007/s00401-010-0770-2 \| PMID = 21069360 }}</ref>
	*Astrocytoma		*Astrocytoma.
	*Oligodendroglioma		*Oligodendroglioma (requirement for diagnosis).
	*Secondary Glioblastoma		*Secondary Glioblastoma.

	Less common:		Less common:

Jensflorian: /* General */ Esthesioneuroblastoma

2019-10-22T06:35:59Z

General: Esthesioneuroblastoma

← Older revision		Revision as of 06:35, 22 October 2019
Line 10:		Line 10:
	*Myeloproliferative disorders<ref>{{Cite journal \| last1 = Andrulis \| first1 = M. \| last2 = Capper \| first2 = D. \| last3 = Luft \| first3 = T. \| last4 = Hartmann \| first4 = C. \| last5 = Zentgraf \| first5 = H. \| last6 = von Deimling \| first6 = A. \| title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. \| journal = Leuk Res \| volume = 34 \| issue = 8 \| pages = 1091-3 \| month = Aug \| year = 2010 \| doi = 10.1016/j.leukres.2010.02.014 \| PMID = 20227112 }}</ref>		*Myeloproliferative disorders<ref>{{Cite journal \| last1 = Andrulis \| first1 = M. \| last2 = Capper \| first2 = D. \| last3 = Luft \| first3 = T. \| last4 = Hartmann \| first4 = C. \| last5 = Zentgraf \| first5 = H. \| last6 = von Deimling \| first6 = A. \| title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. \| journal = Leuk Res \| volume = 34 \| issue = 8 \| pages = 1091-3 \| month = Aug \| year = 2010 \| doi = 10.1016/j.leukres.2010.02.014 \| PMID = 20227112 }}</ref>
	*Cholangiocellular carcinoma<ref>{{Cite journal \| last1 = Zou \| first1 = S. \| last2 = Li \| first2 = J. \| last3 = Zhou \| first3 = H. \| last4 = Frech \| first4 = C. \| last5 = Jiang \| first5 = X. \| last6 = Chu \| first6 = JS. \| last7 = Zhao \| first7 = X. \| last8 = Li \| first8 = Y. \| last9 = Li \| first9 = Q. \| title = Mutational landscape of intrahepatic cholangiocarcinoma. \| journal = Nat Commun \| volume = 5 \| issue = \| pages = 5696 \| month = Dec \| year = 2014 \| doi = 10.1038/ncomms6696 \| PMID = 25526346 }}</ref>		*Cholangiocellular carcinoma<ref>{{Cite journal \| last1 = Zou \| first1 = S. \| last2 = Li \| first2 = J. \| last3 = Zhou \| first3 = H. \| last4 = Frech \| first4 = C. \| last5 = Jiang \| first5 = X. \| last6 = Chu \| first6 = JS. \| last7 = Zhao \| first7 = X. \| last8 = Li \| first8 = Y. \| last9 = Li \| first9 = Q. \| title = Mutational landscape of intrahepatic cholangiocarcinoma. \| journal = Nat Commun \| volume = 5 \| issue = \| pages = 5696 \| month = Dec \| year = 2014 \| doi = 10.1038/ncomms6696 \| PMID = 25526346 }}</ref>
			*Esthesioneuroblastoma.<ref>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Engel \| first2 = NW. \| last3 = Stichel \| first3 = D. \| last4 = Lechner \| first4 = M. \| last5 = Glöss \| first5 = S. \| last6 = Schmid \| first6 = S. \| last7 = Koelsche \| first7 = C. \| last8 = Schrimpf \| first8 = D. \| last9 = Niesen \| first9 = J. \| title = DNA methylation-based reclassification of olfactory neuroblastoma. \| journal = Acta Neuropathol \| volume = 136 \| issue = 2 \| pages = 255-271 \| month = 08 \| year = 2018 \| doi = 10.1007/s00401-018-1854-7 \| PMID = 29730775 }}</ref>

	===Molecular background===		===Molecular background===

Jensflorian: update

2018-03-21T10:28:14Z

update

← Older revision		Revision as of 10:28, 21 March 2018
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	===Diagnosis===		===Diagnosis===
	*(Pyro)sequencing of exon4 IDH1/2		*(Pyro)sequencing of exon4 IDH1/2
	*Mutation-specific antibody for the most common [[IDH-1]] R132H mutation.		* Mutation-specific antibody for the most common [[IDH-1]] R132H mutation available.
			* IDH1 mutations are far more common than IDH2 mutations in glioma.

	==See also==		==See also==
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	{{Reflist\|1}}		{{Reflist\|1}}

	[[Category:Molecular pathology]][[Neuropathology]]		[[Category:Molecular pathology]][[Category:Neuropathology]]

Jensflorian: /* General */ update

2018-03-21T10:23:03Z

General: update

← Older revision		Revision as of 10:23, 21 March 2018
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	*Cholangiocellular carcinoma<ref>{{Cite journal \| last1 = Zou \| first1 = S. \| last2 = Li \| first2 = J. \| last3 = Zhou \| first3 = H. \| last4 = Frech \| first4 = C. \| last5 = Jiang \| first5 = X. \| last6 = Chu \| first6 = JS. \| last7 = Zhao \| first7 = X. \| last8 = Li \| first8 = Y. \| last9 = Li \| first9 = Q. \| title = Mutational landscape of intrahepatic cholangiocarcinoma. \| journal = Nat Commun \| volume = 5 \| issue = \| pages = 5696 \| month = Dec \| year = 2014 \| doi = 10.1038/ncomms6696 \| PMID = 25526346 }}</ref>		*Cholangiocellular carcinoma<ref>{{Cite journal \| last1 = Zou \| first1 = S. \| last2 = Li \| first2 = J. \| last3 = Zhou \| first3 = H. \| last4 = Frech \| first4 = C. \| last5 = Jiang \| first5 = X. \| last6 = Chu \| first6 = JS. \| last7 = Zhao \| first7 = X. \| last8 = Li \| first8 = Y. \| last9 = Li \| first9 = Q. \| title = Mutational landscape of intrahepatic cholangiocarcinoma. \| journal = Nat Commun \| volume = 5 \| issue = \| pages = 5696 \| month = Dec \| year = 2014 \| doi = 10.1038/ncomms6696 \| PMID = 25526346 }}</ref>

			===Molecular background===
			* IDH are present as homodimers and oxidize isocitrate to alpha-ketoglutarate.
			* Heterozygous IDH mutations result in reduction of alpha-ketoglutrate to D-2-hydroxyglutarate.
			* D-2-hydroxyglutarate blocks histone demethylation and promotes proliferation.
			* The increased D-2-hydroxyglutarate can be detected by Proton magnetic resonance spectroscopy.<ref>{{Cite journal \| last1 = Choi \| first1 = C. \| last2 = Raisanen \| first2 = JM. \| last3 = Ganji \| first3 = SK. \| last4 = Zhang \| first4 = S. \| last5 = McNeil \| first5 = SS. \| last6 = An \| first6 = Z. \| last7 = Madan \| first7 = A. \| last8 = Hatanpaa \| first8 = KJ. \| last9 = Vemireddy \| first9 = V. \| title = Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma. \| journal = J Clin Oncol \| volume = 34 \| issue = 33 \| pages = 4030-4039 \| month = Nov \| year = 2016 \| doi = 10.1200/JCO.2016.67.1222 \| PMID = 28248126 }}</ref>

	===Implication===		===Implication===
	*IDH mutant gliomas have a more favourable outcome than wildtype tumors<ref>{{Cite journal \| last1 = Hartmann \| first1 = C. \| last2 = Hentschel \| first2 = B. \| last3 = Wick \| first3 = W. \| last4 = Capper \| first4 = D. \| last5 = Felsberg \| first5 = J. \| last6 = Simon \| first6 = M. \| last7 = Westphal \| first7 = M. \| last8 = Schackert \| first8 = G. \| last9 = Meyermann \| first9 = R. \| title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. \| journal = Acta Neuropathol \| volume = 120 \| issue = 6 \| pages = 707-18 \| month = Dec \| year = 2010 \| doi = 10.1007/s00401-010-0781-z \| PMID = 21088844 }}</ref>		*IDH mutant gliomas have a more favourable outcome than wildtype tumors<ref>{{Cite journal \| last1 = Hartmann \| first1 = C. \| last2 = Hentschel \| first2 = B. \| last3 = Wick \| first3 = W. \| last4 = Capper \| first4 = D. \| last5 = Felsberg \| first5 = J. \| last6 = Simon \| first6 = M. \| last7 = Westphal \| first7 = M. \| last8 = Schackert \| first8 = G. \| last9 = Meyermann \| first9 = R. \| title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. \| journal = Acta Neuropathol \| volume = 120 \| issue = 6 \| pages = 707-18 \| month = Dec \| year = 2010 \| doi = 10.1007/s00401-010-0781-z \| PMID = 21088844 }}</ref>
	*Within IDH mutant tumors, conventional grading is not represented by diffent survival.<ref>{{Cite journal \| last1 = Reuss \| first1 = DE. \| last2 = Mamatjan \| first2 = Y. \| last3 = Schrimpf \| first3 = D. \| last4 = Capper \| first4 = D. \| last5 = Hovestadt \| first5 = V. \| last6 = Kratz \| first6 = A. \| last7 = Sahm \| first7 = F. \| last8 = Koelsche \| first8 = C. \| last9 = Korshunov \| first9 = A. \| title = IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. \| journal = Acta Neuropathol \| volume = 129 \| issue = 6 \| pages = 867-73 \| month = Jun \| year = 2015 \| doi = 10.1007/s00401-015-1438-8 \| PMID = 25962792 }}</ref>		*Within IDH mutant tumors, conventional grading is not represented by diffent survival.<ref>{{Cite journal \| last1 = Reuss \| first1 = DE. \| last2 = Mamatjan \| first2 = Y. \| last3 = Schrimpf \| first3 = D. \| last4 = Capper \| first4 = D. \| last5 = Hovestadt \| first5 = V. \| last6 = Kratz \| first6 = A. \| last7 = Sahm \| first7 = F. \| last8 = Koelsche \| first8 = C. \| last9 = Korshunov \| first9 = A. \| title = IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. \| journal = Acta Neuropathol \| volume = 129 \| issue = 6 \| pages = 867-73 \| month = Jun \| year = 2015 \| doi = 10.1007/s00401-015-1438-8 \| PMID = 25962792 }}</ref>
	*~~The IDH hotspot~~ mutations ~~result~~ in ~~increased 2-hydroxyglutarate which can be detected by Proton magnetic resonance spectroscopy~~.~~<ref>{{Cite journal~~ \| last1 = Choi \| first1 = C. \| last2 = Raisanen \| first2 = JM. \| last3 = Ganji \| first3 = SK. \| last4 = Zhang \| first4 = S. \| last5 = McNeil \| first5 = SS. \| last6 = An \| first6 = Z. \| last7 = Madan \| first7 = A. \| last8 = Hatanpaa \| first8 = KJ. \| last9 = Vemireddy \| first9 = V. \| title = Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma. \| journal = J Clin Oncol \| volume = 34 \| issue = 33 \| pages = 4030-4039 \| month = Nov \| year = 2016 \| doi = 10.1200/JCO.2016.67.1222 \| PMID = 28248126 }}</ref>
			*IDH1 and IDH2 mutations are mutually exclusive.
			*IDH2 mutations are more common in oligodendroglial tumors.

Jensflorian: created

2017-03-22T13:24:04Z

created

New page

'''IDH mutation''' is a re-occuring theme in [[molecular neuropathology]]. IDH is an [[oncometabolite]]. Mutations are located at hotspot positions in IDH R132, IDH2 R140 or IDH2 R172.<ref name=omim147700 >{{OMIM|147700}}</ref> <ref name=omim147650 >{{OMIM|147650}}</ref>

==General==
Seen in:<ref>{{Cite journal | last1 = Capper | first1 = D. | last2 = Reuss | first2 = D. | last3 = Schittenhelm | first3 = J. | last4 = Hartmann | first4 = C. | last5 = Bremer | first5 = J. | last6 = Sahm | first6 = F. | last7 = Harter | first7 = PN. | last8 = Jeibmann | first8 = A. | last9 = von Deimling | first9 = A. | title = Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology. | journal = Acta Neuropathol | volume = 121 | issue = 2 | pages = 241-52 | month = Feb | year = 2011 | doi = 10.1007/s00401-010-0770-2 | PMID = 21069360 }}</ref>
*Astrocytoma
*Oligodendroglioma
*Secondary Glioblastoma

Less common:
*Myeloproliferative disorders<ref>{{Cite journal | last1 = Andrulis | first1 = M. | last2 = Capper | first2 = D. | last3 = Luft | first3 = T. | last4 = Hartmann | first4 = C. | last5 = Zentgraf | first5 = H. | last6 = von Deimling | first6 = A. | title = Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing. | journal = Leuk Res | volume = 34 | issue = 8 | pages = 1091-3 | month = Aug | year = 2010 | doi = 10.1016/j.leukres.2010.02.014 | PMID = 20227112 }}</ref>
*Cholangiocellular carcinoma<ref>{{Cite journal | last1 = Zou | first1 = S. | last2 = Li | first2 = J. | last3 = Zhou | first3 = H. | last4 = Frech | first4 = C. | last5 = Jiang | first5 = X. | last6 = Chu | first6 = JS. | last7 = Zhao | first7 = X. | last8 = Li | first8 = Y. | last9 = Li | first9 = Q. | title = Mutational landscape of intrahepatic cholangiocarcinoma. | journal = Nat Commun | volume = 5 | issue = | pages = 5696 | month = Dec | year = 2014 | doi = 10.1038/ncomms6696 | PMID = 25526346 }}</ref>

===Implication===
*IDH mutant gliomas have a more favourable outcome than wildtype tumors<ref>{{Cite journal | last1 = Hartmann | first1 = C. | last2 = Hentschel | first2 = B. | last3 = Wick | first3 = W. | last4 = Capper | first4 = D. | last5 = Felsberg | first5 = J. | last6 = Simon | first6 = M. | last7 = Westphal | first7 = M. | last8 = Schackert | first8 = G. | last9 = Meyermann | first9 = R. | title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. | journal = Acta Neuropathol | volume = 120 | issue = 6 | pages = 707-18 | month = Dec | year = 2010 | doi = 10.1007/s00401-010-0781-z | PMID = 21088844 }}</ref>
*Within IDH mutant tumors, conventional grading is not represented by diffent survival.<ref>{{Cite journal | last1 = Reuss | first1 = DE. | last2 = Mamatjan | first2 = Y. | last3 = Schrimpf | first3 = D. | last4 = Capper | first4 = D. | last5 = Hovestadt | first5 = V. | last6 = Kratz | first6 = A. | last7 = Sahm | first7 = F. | last8 = Koelsche | first8 = C. | last9 = Korshunov | first9 = A. | title = IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. | journal = Acta Neuropathol | volume = 129 | issue = 6 | pages = 867-73 | month = Jun | year = 2015 | doi = 10.1007/s00401-015-1438-8 | PMID = 25962792 }}</ref>
*The IDH hotspot mutations result in increased 2-hydroxyglutarate which can be detected by Proton magnetic resonance spectroscopy.<ref>{{Cite journal | last1 = Choi | first1 = C. | last2 = Raisanen | first2 = JM. | last3 = Ganji | first3 = SK. | last4 = Zhang | first4 = S. | last5 = McNeil | first5 = SS. | last6 = An | first6 = Z. | last7 = Madan | first7 = A. | last8 = Hatanpaa | first8 = KJ. | last9 = Vemireddy | first9 = V. | title = Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma. | journal = J Clin Oncol | volume = 34 | issue = 33 | pages = 4030-4039 | month = Nov | year = 2016 | doi = 10.1200/JCO.2016.67.1222 | PMID = 28248126 }}</ref>

===Diagnosis===
*(Pyro)sequencing of exon4 IDH1/2
*Mutation-specific antibody for the most common [[IDH-1]] R132H mutation.

==See also==
*[[Molecular pathology]].
*[[Neuropathology]]

==References==
{{Reflist|1}}

[[Category:Molecular pathology]][[Neuropathology]]