NcXHF

RETHINKING TREATMENT FOR CHONDROSARCOMA: A ROLE FOR IDH INHIBITION?
drosarcoma and is associated with adverse outcome. Am J Surg Pathol.
2001;25:1520-1527.
69. Grignani G, Palmerini E, Stacchiotti S, et al. A phase 2 trial of imatinib
mesylate in patients with recurrent nonresectable chondrosarcomas
expressing platelet-derived growth factor receptor- or -: an Italian
Sarcoma Group study. Cancer. 2011;117:826-831.
70. Tsuda M, Takahashi S, Takahashi Y, et al. Transcriptional coactivators
CREB-binding protein and p300 regulate chondrocytespecifıc
gene expression via association with Sox9. J Biol Chem. 2003;
278:27224-27229.
71. Liu CJ, Prazak L, Fajardo M, et al. Leukemia/lymphoma-related factor,
a POZ domain-containing transcriptional repressor, interacts with histone
deacetylase-1 and inhibits cartilage oligomeric matrix protein
gene expression and chondrogenesis. J Biol Chem. 2004;279:47081-
47091.
72. Villar-Garea A, Esteller M. Histone deacetylase inhibitors: understanding
a new wave of anticancer agents. Intl J Cancer. 2004;112:171-
178.
73. Sakimura R, Tanaka K, Nakatani F, et al. Antitumor effects of histone
deacetylase inhibitor on Ewing’s family tumors. Intl J Cancer. 2005;
116:784-792.
74. Sakimura R, Tanaka K, Yamamoto S, et al. The effects of histone
deacetylase inhibitors on the induction of differentiation in chondrosarcoma
cells. Clin Cancer Res. 2007;13:275-282.
75. Leonardi R, Subramanian C, Jackowski S, et al. Cancer-associated isocitrate
dehydrogenase mutations inactivate NADPH-dependent reductive
carboxylation. J Biol Chem. 2012;287:14615-14620.
76. Geisbrecht BV, Gould SJ. The human PICD gene encodes a cytoplasmic
and peroxisomal NADP()-dependent isocitrate dehydrogenase.
J Biol Chem. 1999;274:30527-30533.
77. Yoshihara T, Hamamoto T, Munakata R, et al. Localization of cytosolic
NADP-dependent isocitrate dehydrogenase in the peroxisomes of rat
liver cells: biochemical and immunocytochemical studies. J Histochem
Cytochem. 2001;49:1123-1131.
78. Wang F, Travins J, DeLaBarre B, et al. Targeted inhibition of mutant
IDH2 in leukemia cells induces cellular differentiation. Science. 2013;
340:622-626.
79. Narahara K, Kimura S, Kikkawa K, et al. Probable assignment of soluble
isocitrate dehydrogenase (IDH1) to 2q33.3. Hum Genet. 1985;71:
37-40.
80. Oh IU, Inazawa J, Kim YO, et al. Assignment of the human mitochondrial
NADP()-specifıc isocitrate dehydrogenase (IDH2) gene to
15q26.1 by in situ hybridization. Genomics. 1996;38:104-106.
81. Sjöblom T, Jones S, Wood LD, et al. The consensus coding sequences of
human breast and colorectal cancers. Science. 2006;314:268-274.
82. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas.
N Engl J Med. 2009;360:765-773.
83. Kosmider O, Gelsi-Boyer V, Slama L, et al. Mutations of IDH1 and
IDH2 genes in early and accelerated phases of myelodysplastic syndromes
and MDS/myeloproliferative neoplasms. Leukemia. 2010;24:
1094-1096.
84. Marcucci G, Maharry K, Wu YZ, et al. IDH1 and IDH2 gene mutations
identify novel molecular subsets within de novo cytogenetically normal
acute myeloid leukemia: a Cancer and Leukemia Group B study.
J Clin Oncol. 2010;28:2348-2355.
85. Schaap FG, French PJ, Bovée JV. Mutations in the isocitrate dehydrogenase
genes IDH1 and IDH2 in tumors. Adv Anat Pathol. 2013;
20:32-38.
86. Amary MF, Bacsi K, Maggiani F, et al. IDH1 and IDH2 mutations are
frequent events in central chondrosarcoma and central and periosteal
chondromas but not in other mesenchymal tumours. J Pathol. 2011;
224:334-343.
87. Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by
sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;
361:1058-1066.
88. Schnittger S, Haferlach C, Ulke M, et al. IDH1 mutations are detected
in 6.6% of 1414 AML patients and are associated with intermediate risk
karyotype and unfavorable prognosis in adults younger than 60 years
and unmutated NPM1 status. Blood. 2010;116:5486-5496.
89. Patel KP, Ravandi F, Ma D, et al. Acute myeloid leukemia with IDH1 or
IDH2 mutation: frequency and clinicopathologic features. Am J Clin
Pathol. 2011;135:35-45.
90. Chou WC, Lei WC, Ko BS, et al. The prognostic impact and stability of
Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid
leukemia. Leukemia. 2011;25:246-253.
91. Zhao S, Lin Y, Xu W, et al. Glioma-derived mutations in IDH1 dominantly
inhibit IDH1 catalytic activity and induce HIF-1alpha. Science.
2009;324:261-265.
92. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations
produce 2-hydroxyglutarate. Nature. 2009;462:739-744.
93. Luchman HA, Stechishin OD, Dang NH, et al. An in vivo patientderived
model of endogenous IDH1-mutant glioma. Neuro Oncol.
2012;14:184-191.
94. Ward PS, Patel J, Wise DR, et al. The common feature of leukemiaassociated
IDH1 and IDH2 mutations is a neomorphic enzyme activity
converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell.
2010;17:225-234.
95. Welch JS, Ley TJ, Link DC, et al. The origin and evolution of mutations
in acute myeloid leukemia. Cell. 2012;150:264-278.
96. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2
mutations result in a hypermethylation phenotype, disrupt TET2
function, and impair hematopoietic differentiation. Cancer Cell. 2010;
18:553-567.
97. Hartmann C, Meyer J, Balss J, et al. Type and frequency of IDH1 and
IDH2 mutations are related to astrocytic and oligodendroglial differentiation
and age: a study of 1,010 diffuse gliomas. Acta Neuropathol.
2009;118:469-474.
98. Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation
and results in a block to cell differentiation. Nature. 2012;
483:474-478.
99. Koivunen P, Lee S, Duncan CG, et al. Transformation by the (R)-
enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature.
2012;483:484-488.
100. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a
competitive inhibitor of -ketoglutarate-dependent dioxygenases.
Cancer Cell. 2011;19:17-30.
101. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identifıcation of a
CpG island methylator phenotype that defınes a distinct subgroup of
glioma. Cancer Cell. 2010;17:510-522.
102. Gross S, Cairns RA, Minden MD, et al. Cancer-associated metabolite
2-hydroxyglutarate accumulates in acute myelogenous leukemia with
isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010;207:339-
344.
103. Fathi AT, Sadrzadeh H, Borger DR, et al. Prospective serial evaluation
of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid
leukemia, to assess disease activity and therapeutic response.
Blood. 2012;120:4649-4652.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK
e655