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 640 publications

(654 citation statements)

References 90 publications

Supporting

Mentioning

625

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

show abstract

“…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%