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Diagnostic utility of IDH1/2 mutations to distinguish dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone

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TLDR
In this article, an IDH1 or IDH2 mutation signature was used as a clinically diagnostic marker for the distinction of dedifferentiated component of chondrosarcoma from UPS of bone.
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This article is published in Human Pathology.The article was published on 2017-07-01 and is currently open access. It has received 35 citations till now. The article focuses on the topics: Chondrosarcoma & Undifferentiated Pleomorphic Sarcoma.

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The epigenomics of sarcoma.

TL;DR: How the disease biology of many sarcomas is driven by chromatin pathway alterations ranging from dysregulation of DNA methylation, histone modifications and nucleosome remodelling to disruption of higher-order, 3D chromatin structure is discussed with a view to better develop targeted therapies for patients with sarcoma.
Journal ArticleDOI

IDH1/2 Mutations Predict Shorter Survival in Chondrosarcoma.

TL;DR: In CHS, IDH1/2-mutation status and the histological aggressiveness of the CHS are important predictors for OS, and the R140 IDH2 may also be a novel target for the treatment of CHS patients.
Journal ArticleDOI

H3K27me3 deficiency defines a subset of dedifferentiated chondrosarcomas with characteristic clinicopathological features.

TL;DR: H3K27me3 deficiency defines a novel subset of dedifferentiated chondrosarcoma that requires recognition because of its diagnostic and potential clinical implications, and targeted next generation sequencing identified an IDH2 mutation in one case and COL2A1 truncations in three cases.
Journal ArticleDOI

Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone.

TL;DR: This study represents the first comprehensive WES and RNA‐Seq analysis of UPSb tumours revealing novel protein‐coding recurrent gene mutations, gene fusions and identifying a potential UPSb molecular biomarker, thereby broadening the understanding of the pathogenic mechanisms and highlighting the possibility of developing novel targeted therapeutics.
Journal ArticleDOI

Chondrosarcoma-from Molecular Pathology to Novel Therapies

TL;DR: In this article, a multidisciplinary characterization of CHS from its pathology to therapies is presented, where the morphology of each subtype with the role of immunohistochemical markers in diagnostics is discussed.
References
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Journal ArticleDOI

Fast and accurate short read alignment with Burrows–Wheeler transform

TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
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The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate

TL;DR: It is reported that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML), and AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis.
Journal ArticleDOI

Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing

TL;DR: Exome and genome sequences and whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases, which are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.
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Frequently Asked Questions (11)
Q1. What are the contributions in "Diagnostic utility of idh1/2 mutations to distinguish dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone" ?

The most common morphological pattern of the dedifferentiated component is undifferentiated pleomorphic sarcoma ( UPS ), so-called malignant fibrous histiocytoma ( MFH ) this paper. 

If effective IDH1/2 mutation inhibitors become available in the future, PCR mutation analysis on cases of dedifferentiated chondrosarcoma help guide treatment decisions. 

IDH is an important homodimeric enzyme in the citric acid cycle (the Krebs cycle) and normally catalyzes the decarboxylation of isocitrate (ICT) to α–ketoglutarate (α-KG). 

Recent in vitro study revealed that high doses of IDH1 inhibitor AGI-5198 inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis using chondrosarcoma cell lines, which revealed anti-tumor activity of the IDH1 inhibitor (17). 

a malignant cartilaginous tumor, is the second most common primary malignancy of bone after osteosarcoma, often arising from the pelvis, femur, or humerus. 

One potential drawback of performing mutational analysis on bone tumors is that the decalcification procedure involves hydrochloric acid which is known to cause DNA damage through chemical hydrolysis which has been previously discussed by Kerr and colleagues in their analysis of IDH1/2 mutations in chondoblastic osteosarcoma (15) Consequently, tumor sections with significant bone matrix may be subjected to this process, often rendering them unsuitable for these studies. 

Although the IDH1 R132H mutation occurs in approximately 70% of WHO grade II and III gliomas (7), it was detected in only 17% of the IDH 1/2 mutations present in cartilaginous tumors in one study (14) and 0% (0/14 positive cases) in another study (15). 

A total of 68 cases were collected for IDH1/2 mutation analysis and included 31 conventional chondrosarcomas, 23 dedifferentiated chondrosarcomas, and 14 UPS of bone. 

While the IDH1 R132H monoclonal antibody appears to be a reliable surrogate for mutation status, the low rate of its prevalence in dedifferentiated chondrosarcoma limits its usefulness in this setting. 

Dedifferentiated chondrosarcoma is a highly aggressive biphasic mesenchymal tumor consisting of a well-differentiated cartilaginous component admixed with area of high-grade sarcoma. 

Samples were classified as mutation-positive (IDH1 Mut R132, IDH2 Mut R172, and IDH1 Mut R100) if the ΔCT value was less than or equal to the ΔCT cutoff value of the respective mutation detection assay.