IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain.

dc.contributor.author

Lopez, Giselle Y

dc.contributor.author

Reitman, Zachary J

dc.contributor.author

Solomon, David

dc.contributor.author

Waldman, Todd

dc.contributor.author

Bigner, Darell D

dc.contributor.author

McLendon, Roger E

dc.contributor.author

Rosenberg, Steven A

dc.contributor.author

Samuels, Yardena

dc.contributor.author

Yan, Hai

dc.date.accessioned

2019-01-02T22:29:06Z

dc.date.available

2019-01-02T22:29:06Z

dc.date.issued

2010-07-13

dc.date.updated

2019-01-02T22:29:06Z

dc.description.abstract

Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). IDH1/2 were recently identified as mutated in a large percentage of progressive gliomas. These mutations occur at IDH1(R132) or the homologous IDH2(R172). Melanomas share some genetic features with IDH1/2-mutated gliomas, such as frequent TP53 mutation. We sought to test whether melanoma is associated with IDH1/2 mutations. Seventy-eight human melanoma samples were analyzed for IDH1(R132) and IDH2(R172) mutation status. A somatic, heterozygous IDH1 c.C394T (p.R132C) mutation was identified in one human melanoma metastasis to the lung. Having identified this mutation in one metastasis, we sought to test the hypothesis that certain selective pressures in the brain environment may specifically favor the cell growth or survival of tumor cells with mutations in IDH1/2, regardless of primary tumor site. To address this, we analyzed IDH1(R132) and IDH2(R172) mutation status 53 metastatic brain tumors, including nine melanoma metastases. Results revealed no mutations in any samples. This lack of mutations would suggest that mutations in IDH1(R132) or IDH2(R172) may be necessary for the formation of tumors in a cell-lineage dependent manner, with a particularly strong selective pressure for mutations in progressive gliomas; this also suggests the lack of a particular selective pressure for growth in brain tissue in general. Studies on the cell-lineages of tumors with IDH1/2 mutations may help clarify the role of these mutations in the development of brain tumors.

dc.identifier

S0006-291X(10)01282-9

dc.identifier.issn

0006-291X

dc.identifier.issn

1090-2104

dc.identifier.uri

https://hdl.handle.net/10161/17845

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

Biochemical and biophysical research communications

dc.relation.isversionof

10.1016/j.bbrc.2010.06.125

dc.subject

Humans

dc.subject

Melanoma

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Brain Neoplasms

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Skin Neoplasms

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Lung Neoplasms

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Neoplasm Metastasis

dc.subject

Isocitrate Dehydrogenase

dc.subject

Mutation

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Middle Aged

dc.subject

Female

dc.subject

Selection, Genetic

dc.title

IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain.

dc.type

Journal article

duke.contributor.orcid

Lopez, Giselle Y|0000-0001-5435-6668

duke.contributor.orcid

Reitman, Zachary J|0000-0002-9122-9550

duke.contributor.orcid

Bigner, Darell D|0000-0001-5548-4899

duke.contributor.orcid

McLendon, Roger E|0000-0001-6682-4588

duke.contributor.orcid

Yan, Hai|0000-0001-9509-8431

pubs.begin-page

585

pubs.end-page

587

pubs.issue

3

pubs.organisational-group

School of Medicine

pubs.organisational-group

Duke

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Pathology

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Surgery

pubs.organisational-group

Neurosurgery

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

Basic Science Departments

pubs.publication-status

Published

pubs.volume

398

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