Chordoma: current concepts, management, and future directions

Walcott, Brian P.; Nahed, Brian V.; Mohyeldin, Ahmed; Coumans, Jean-Valéry; Kahle, Kristopher T.; Ferreira, Manuel

doi:10.1016/s1470-2045(11)70337-0

Cited by 620 publications

(654 citation statements)

References 90 publications

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“…Local recurrence rate is high and 5 y survival rate is approximately 60%. 1,2 Due to the rarity of the samples and difficulty in obtaining appropriate control tissues, there is a paucity of genetic and, even more, epigenetic studies reported in the literature (reviewed in Yakkioui et al 3 and references within). Expression of brachyury (T) has been proposed as a diagnostic marker for chordomas and plays a critical role in chordoma biology.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas

et al. 2015

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Chordomas are an aggressive rare type of malignant bone tumors arising from the remnant of the notochord. Chordomas occur mainly in vertebral bones and account for 1-4% of malignant bone tumors. Management and treatment of chordomas are difficult as they are resistant to conventional chemotherapy; therefore, they are mainly treated with surgery and radiation therapy. In this study, we performed DNA methylation profiling of 26 chordomas and normal nucleus pulposus samples plus UCH-1 chordoma cell line using the Illumina Infinium HumanMethylation450 BeadChips. Combined bisulfite restriction analysis and bisulfite sequencing was used to confirm the methylation data. Gene expression was analyzed using RT-PCR before and after 5-aza-2'-deoxycytidine (5-azaDC) treatment of chordoma cell lines. Analysis of the HumanMethylation450 BeadChip data led to the identification of 8,819 loci (2.9%) that were significantly differentially methylated (>0.2 average b-value difference) between chordomas and nucleus pulposus samples (adjusted P < 0.05). Among these, 5,868 probes (66.5%) were hypomethylated, compared to 2,951 (33.5%) loci that were hypermethylated in chordomas compared to controls. From the 2,951 differentially hypermethylated probes, 33.3% were localized in the promoter region (982 probes) and, among these, 104 probes showed cancer-specific hypermethylation. Ingenuity Pathway Analysis indicates that the cancer-specific differentially methylated loci are involved in various networks including cancer disease, nervous system development and function, cell death and survival, cellular growth, cellular development, and proliferation. Furthermore, we identified a subset of probes that were differentially methylated between recurrent and non-recurrent chordomas. BeadChip methylation data was confirmed for these genes and gene expression was shown to be upregulated in methylated chordoma cell lines after treatment with 5-azaDC. Understanding epigenetic changes in chordomas may provide insights into chordoma tumorigenesis and development of epigenetic biomarkers.

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Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas

et al. 2015

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“…Spinal chordomas occur more frequently in the cervical region (20 to 50%) than in the lumbar and thoracic spine 3 . They are commonly located on the midline and are associated with variable and usually marked destruction of one or more vertebral bodies [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Paravertebral High Cervical Chordoma

Elefante

Caranci²,

de³

et al. 2013

Neuroradiol J

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“…Chordoma occurs at skull base in 30-40% of cases. 1,2 Although it is usually a slow growing cancer and looks relatively benign histologically, it is locally aggressive and frequently recurs following treatment. Normally, surgical resection is the first line treatment.…”

Section: Introductionmentioning

confidence: 99%

“…3,6,7 Chordoma has also the potential to metastasize to regional lymph nodes, distant sites and cerebrospinal fluid. 1,2,7,8 A rare and peculiar pattern of failure is tumour seeding along the surgical access pathway that is reported in less than 5% of cases. 8 These sites, such as the nasal cavity and surrounding soft tissue, are often outside the treatment field of radiation and can be subject to iatrogenic tumour implantation.…”

Section: Introductionmentioning

confidence: 99%