Neomorphic mutations create therapeutic challenges in cancer

Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer

(2016) O. Clark et al.   CLINICAL CANCER RESEARCH

Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations

(2015) T. Dogruluk et al.   CANCER RESEARCH

Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling

(2015) Pau Creixell et al.   CELL

Unmasking Determinants of Specificity in the Human Kinome

(2015) Pau Creixell et al.   CELL

Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure

(2015) Lili Gong et al.   CELL CYCLE

Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers

(2015) Sally Temraz et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia

(2015) Ujunwa C Okoye-Okafor et al.   Nature Chemical Biology

Discovery and functional characterization of a neomorphic PTEN mutation

(2015) Helio A. Costa et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Neomorphic effects of recurrent somatic mutations inYin Yang 1in insulin-producing adenomas

(2015) M. Kyle Cromer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting Mutant p53 by a SIRT1 Activator YK-3-237 Inhibits the Proliferation of Triple-Negative Breast Cancer Cells

(2015) Yong Weon Yi et al.   Oncotarget

Naturally Occurring Neomorphic PIK3R1 Mutations Activate the MAPK Pathway, Dictating Therapeutic Response to MAPK Pathway Inhibitors

(2014) Lydia W.T. Cheung et al.   CANCER CELL

Cancer-Associated PTEN Mutants Act in a Dominant-Negative Manner to Suppress PTEN Protein Function

(2014) Antonella Papa et al.   CELL

Combined MEK and PI3K Inhibition in a Mouse Model of Pancreatic Cancer

(2014) B. Alagesan et al.   CLINICAL CANCER RESEARCH

A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations

(2014) Shinji Kohsaka et al.   NATURE GENETICS

Dual Pharmacological Targeting of the MAP Kinase and PI3K/mTOR Pathway in Preclinical Models of Colorectal Cancer

(2014) Todd M. Pitts et al.   PLoS One

Drugging the HDAC6–HSP90 interplay in malignant cells

(2014) Oliver H. Krämer et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Assessing PIK3CA and PTEN in Early-Phase Trials with PI3K/AKT/mTOR Inhibitors

(2014) Filip Janku et al.   Cell Reports

Gain of Interaction with IRS1 by p110α-Helical Domain Mutants Is Crucial for Their Oncogenic Functions

(2013) Yujun Hao et al.   CANCER CELL

PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types

(2013) Carolyn D. Britten   CANCER CHEMOTHERAPY AND PHARMACOLOGY

The Somatic Genomic Landscape of Glioblastoma

(2013) Cameron W. Brennan et al.   CELL

Integrated genomic characterization of endometrial carcinoma

(2013) Gad Getz et al.   NATURE

Mutational landscape and significance across 12 major cancer types

(2013) Cyriac Kandoth et al.   NATURE

Pan-cancer patterns of somatic copy number alteration

(2013) Travis I Zack et al.   NATURE GENETICS

(R)-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible

(2013) J.-A. Losman et al.   SCIENCE

An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells

(2013) D. Rohle et al.   SCIENCE

Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation

(2013) F. Wang et al.   SCIENCE

Allele-Specific p53 Mutant Reactivation

(2012) Xin Yu et al.   CANCER CELL

The Clinical Effect of the Dual-Targeting Strategy Involving PI3K/AKT/mTOR and RAS/MEK/ERK Pathways in Patients with Advanced Cancer

(2012) T. Shimizu et al.   CLINICAL CANCER RESEARCH

Mutant p53: one name, many proteins

(2012) W. A. Freed-Pastor et al.   GENES & DEVELOPMENT

Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma

(2012) Juliya Kalinina et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

IDH mutation impairs histone demethylation and results in a block to cell differentiation

(2012) Chao Lu et al.   NATURE

Comprehensive molecular characterization of human colon and rectal cancer

(2012)   NATURE

2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas

(2012) Changho Choi et al.   NATURE MEDICINE

Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8

(2012) W Yan et al.   ONCOGENE

Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells

(2012) Fabian V. Filipp et al.   Pigment Cell & Melanoma Research

Molecular Mechanism of Mutant p53 Stabilization: The Role of HSP70 and MDM2

(2012) Milena Wiech et al.   PLoS One

Somatic Mutations of PIK3R1 Promote Gliomagenesis

(2012) Steven N. Quayle et al.   PLoS One

PTEN Protein Phosphatase Activity Correlates with Control of Gene Expression and Invasion, a Tumor-Suppressing Phenotype, But Not with AKT Activity

(2012) P. Tibarewal et al.   Science Signaling

Detection of 2-Hydroxyglutarate in IDH-Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy

(2012) O. C. Andronesi et al.   Science Translational Medicine

Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo

(2012) Janeta Popovici-Muller et al.   ACS Medicinal Chemistry Letters

The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data: Figure 1.

(2012) Ethan Cerami et al.   Cancer Discovery

Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases

(2011) Wei Xu et al.   CANCER CELL

Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain

(2011) Junjie U. Guo et al.   CELL

The involvement of the transcription factor Yin Yang 1 in cancer development and progression

(2011) Giancarlo Castellano et al.   CELL CYCLE

PIK3CA mutations in human solid tumors: Role in sensitivity to various therapeutic approaches

(2011) Giovanni Ligresti et al.   CELL CYCLE

SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis

(2011) D Li et al.   CELL DEATH AND DIFFERENTIATION

Oncogene Mutation Profiling of Pediatric Solid Tumors Reveals Significant Subsets of Embryonal Rhabdomyosarcoma and Neuroblastoma with Mutated Genes in Growth Signaling Pathways

(2011) N. Shukla et al.   CLINICAL CANCER RESEARCH

The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases

(2011) Rasheduzzaman Chowdhury et al.   EMBO REPORTS

A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes

(2011) Isabel Rodríguez-Escudero et al.   HUMAN MOLECULAR GENETICS

Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy

(2011) Whitney B. Pope et al.   JOURNAL OF NEURO-ONCOLOGY

FOXO1–FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma

(2011) Jinglan Liu et al.   MODERN PATHOLOGY

DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors

(2011) Y. Jiao et al.   SCIENCE

High Frequency of PIK3R1 and PIK3R2 Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability

(2011) Lydia W.T. Cheung et al.   Cancer Discovery

R132H-mutation of isocitrate dehydrogenase-1 is not sufficient for HIF-1α upregulation in adult glioma

(2010) Susan C. Williams et al.   ACTA NEUROPATHOLOGICA

Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation

(2010) W. C. Chou et al.   BLOOD

The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate

(2010) Patrick S. Ward et al.   CANCER CELL

Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation

(2010) Maria E. Figueroa et al.   CANCER CELL

Yin Yang 1 overexpression in diffuse large B-cell lymphoma is associated with B-cell transformation and tumor progression

(2010) Giancarlo Castellano et al.   CELL CYCLE

Restoration of DNA-binding and growth-suppressive activity of mutant forms of p53 via a PCAF-mediated acetylation pathway

(2010) Ricardo E. Perez et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations

(2010) Stefan Gross et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas

(2009) Christian Hartmann et al.   ACTA NEUROPATHOLOGICA

Prolyl hydroxylases as regulators of cell metabolism: Figure 1

(2009) Houda Boulahbel et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer

(2009) Krishna M. Vasudevan et al.   CANCER CELL

PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers

(2009) S. Wee et al.   CANCER RESEARCH

Blinded by the Light: The Growing Complexity of p53

(2009) Karen H. Vousden et al.   CELL

Mutant p53 Drives Invasion by Promoting Integrin Recycling

(2009) Patricia A.J. Muller et al.   CELL

A Mutant-p53/Smad Complex Opposes p63 to Empower TGFβ-Induced Metastasis

(2009) Maddalena Adorno et al.   CELL

Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers

(2009) Mi Ran Kang et al.   INTERNATIONAL JOURNAL OF CANCER

Yin Yang 1 Modulates Taxane Response in Epithelial Ovarian Cancer

(2009) N. Matsumura et al.   MOLECULAR CANCER RESEARCH

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

(2009) Elaine R. Mardis et al.   NEW ENGLAND JOURNAL OF MEDICINE

IDH1andIDH2Mutations in Gliomas

(2009) Hai Yan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Yin Yang 1 regulates the transcriptional activity of androgen receptor

(2009) Z Deng et al.   ONCOGENE

Regulation of Class IA PI 3-kinases: C2 domain-iSH2 domain contacts inhibit p85/p110  and are disrupted in oncogenic p85 mutants

(2009) H. Wu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural evolution of p53, p63, and p73: Implication for heterotetramer formation

(2009) A. C. Joerger et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1 

(2009) S. Zhao et al.   SCIENCE

An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer

(2008) K. Stemke-Hale et al.   CANCER RESEARCH

Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance

(2008) N. T. Ihle et al.   CANCER RESEARCH

Gene expression profiling of Polycomb, Hox and Meis genes in patients with acute myeloid leukaemia

(2008) Lykke Grubach et al.   EUROPEAN JOURNAL OF HAEMATOLOGY

Transcriptional control of human p53-regulated genes

(2008) Todd Riley et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Small-molecule RETRA suppresses mutant p53-bearing cancer cells through a p73-dependent salvage pathway

(2008) J. E. Kravchenko et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

PTEN-deficient cancers depend on PIK3CB

(2008) S. Wee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

(2008) S. Jones et al.   SCIENCE

An Integrated Genomic Analysis of Human Glioblastoma Multiforme

(2008) D. W. Parsons et al.   SCIENCE

PI(3,4,5)P3 and PI(3,4)P2 levels correlate with PKB/akt phosphorylation at Thr308 and Ser473, respectively; PI(3,4)P2 levels determine PKB activity

(2007) Kewei Ma et al.   CELLULAR SIGNALLING