Microarray Comparative Genomic Hybridization Detection of Copy Number Changes in Desmoplastic Melanoma and Malignant Peripheral Nerve Sheath Tumor

Pryor, Jennifer G.; Brown-Kipphut, Brigette; Iqbal, Anwar; Scott, Glynis

doi:10.1097/dad.0b013e31820dfcbf

Cited by 34 publications

(13 citation statements)

References 16 publications

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“…Several hypoxia-inducible HIF target JmjC enzymes are deregulated in breast and lung cancer. The KDM4 family members of JmjC enzymes, targeting di- and trimethylated H3K36 and H3K9, namely KDM4A, KDM4B and KDM4C are upregulated in breast cancer [160,161,162]. KDM4B has been found to mediate oestrogen stimulated cell proliferation of mammary cancer [163].…”

Section: Hypoxia-dependent Nf-κb Activation In Cancermentioning

confidence: 99%

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

2017

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Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of κ-light-chain-enhancer of activated B cells (NF-κB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-κB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-κB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-κB crosstalk.

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Section: Hypoxia-dependent Nf-κb Activation In Cancermentioning

confidence: 99%

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

2017

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“…KDM4A is down-regulated in bladder cancer [80], and KDM4A and KDM4B are up-regulated in breast cancer and peripheral nerve sheath tumours respectively [67,81]. KDM4B is oestrogen inducible and has been shown to promote oestrogen-stimulated breast cancer proliferation [82].…”

Section: Jmjc Functions In Human Diseasementioning

confidence: 99%

Chromatin and oxygen sensing in the context of JmjC histone demethylases

Shmakova

Batie

Druker

et al. 2014

Biochemical Journal

107

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Responding appropriately to changes in oxygen availability is essential for multicellular organism survival. Molecularly, cells have evolved intricate gene expression programmes to handle this stressful condition. Although it is appreciated that gene expression is co-ordinated by changes in transcription and translation in hypoxia, much less is known about how chromatin changes allow for transcription to take place. The missing link between co-ordinating chromatin structure and the hypoxiainduced transcriptional programme could be in the form of a class of dioxygenases called JmjC (Jumonji C) enzymes, the majority of which are histone demethylases. In the present review, we will focus on the function of JmjC histone demethylases, and how these could act as oxygen sensors for chromatin in hypoxia. The current knowledge concerning the role of JmjC histone demethylases in the process of organism development and human disease will also be reviewed.

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“…The concept of an extended spectrum is also supported by comparative genome hybridization data demonstrating that 67% of desmoplastic melanoma share allelic losses of NF1, which matches the immunophenotypic overlap of desmoplastic melanoma with malignant peripheral nerve sheet tumors. 26,[31][32][33][34] Collectively, these data suggest that spindle cell and desmoplastic melanoma represent discrete diagnostic categories within an extended biological spectrum.…”

Section: The Diagnostic Categories Are Part Of An Extended Biologicalmentioning

confidence: 99%

A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma

et al. 2014

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Spindle cell melanoma and desmoplastic melanoma differ clinically in prognosis and therapeutic implications; however, because of partially overlapping histopathological features, diagnostic distinction of spindle cell from desmoplastic melanoma is not always straightforward. A direct comparison of diagnostic and therapeutic biomarkers has not been performed. Meta-review of the literature discloses key clinicopathological differences between spindle cell and desmoplastic melanoma, including immunophenotypes. Using 50 biomarkers available in routine diagnostics, we examined 38 archival cases (n ¼ 16 spindle, 18 desmoplastic, 4 mixed spindle/desmoplastic melanoma). S100 remains as the most reliable routine marker to reach the diagnosis of melanoma in spindle cell and desmoplastic melanoma. We identified nine distinctly labeling markers with spindle cell melanoma showing positivity for laminin, p75, HMB45, c-kit, and MelanA, and desmoplastic melanoma preferentially labeling with collagen IV, trichrome, CD68, and MDM2. On the basis of comparisons of test performance measures, MelanA and trichrome were used to devise a 94% sensitive diagnostic algorithm for the distinction of desmoplastic from spindle cell melanoma. Gene amplification and expression status was assessed for a set of potentially drugable targets (HER2, EGFR, MET, MDM2, TP53, ALK, MYC, FLI-1, and KIT). Fluorescent in situ hybridizations did not reveal a significant number of gene aberrations/rearrangements; however, protein overexpression for at least one of these markers was identified in 35 of 38 cases (92%). In addition, we found BRAF mutations in 31% of spindle cell and 5% of desmoplastic melanoma, with an overall mutation frequency of 16% (n ¼ 6/38). We present the first comprehensive screening study of diagnostic and therapeutic biomarkers in spindle cell and desmoplastic melanoma. The devised algorithm allows diagnostic distinction of desmoplastic from spindle cell melanoma when routine histology is not decisive.

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Microarray Comparative Genomic Hybridization Detection of Copy Number Changes in Desmoplastic Melanoma and Malignant Peripheral Nerve Sheath Tumor

Cited by 34 publications

References 16 publications

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

Chromatin and oxygen sensing in the context of JmjC histone demethylases

A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma

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