The Harris Center serves as key hub for translational research - research programs focus on understanding pathways that contribute to tumor growth, identifying bio-markers and small molecule therapuetics

Ramnik Xavier, MD

Chordoma is a rare, slow-growing malignant tumor believed to arise from cellular remnants of the notochord. The treatment of chordomas is difficult. Wide surgical excision is desirable, but it is rarely feasible based on the anatomic location of the tumor at the base of the skull or the base of the spine.

Currently there are no effective drugs for chordoma, and there are no drugs currently approved to treat chordoma. Unlike with other types of sarcoma, there is no specific known tumor-suppressor gene or oncogene associated with chordoma.

There is a need, however, for understanding the molecular biology of chordoma. We have obtained a number of chordoma cell lines. Most importantly, the Massachusetts General Hospital Sarcoma Group has archived more than 150 cases of chordoma tissues and paraffin blocks in our tissue bank.  DNA, RNA and protein samples from chordoma tumor tissues will be analyzed by CGH or SNP array, gene and protein expression profile with the hope of identification of chordoma susceptibility genes or pathways.

The new discoveries from these studies will identify potential tumor-suppressor genes and oncogenes, then proteins for testing in chordoma tissues.  We plan to determine the efficacy of targeting mTOR, Stat3 expression in chordoma cells by small molecular compounds, siRNA and to evaluate its effect on chordoma cell growth, proliferation and apoptosis.

Our goal is to be able to identify new molecular targets, assess new therapeutics, and better characterize the prognosis of chordomas.

Recent Chordoma Studies

The following articles are a selection of publications from Harris Center researchers from 2000 to 2014, arranged in chronological order with the most recent at the top. Click on a title for the PubMed summary of the article.

How Does the Level of Nerve Root Resection in En Bloc Sacrectomy Influence Patient-Reported Outcomes? van Wulfften Palthe OD1, Houdek MT, Rose PS, Yaszemski MJ, Sim FH, Boland PJ, Healey JH , Hornicek FJ, Schwab JH, Clin Orthop Relat Res. 2016 Mar 18

Characteristics and Patterns of Metastatic Disease from Chordoma Young VA, Curtis KM, Temple HT, Eismont FJ, DeLaney TF, Hornicek FJ, Sarcoma. 2015;2015:517657.

CSPG4 as a prognostic biomarker in chordoma Schoenfeld AJ, Wang X, Wang Y, Hornicek FJ, Nielsen GP, Duan Z, Ferrone S, Schwab JH. Spine J. 2015 Dec 9. pii: S1529-9430(15)

Chordoma: an update on the pathophysiology and molecular mechanisms Sun X, Hornicek F, Schwab JH. Curr Rev Musculoskelet Med. 2015 Dec;8(4):344-52.

High-dose proton-based radiation therapy in the management of spine chordomas: outcomes and clinicopathological prognostic factors.Rotondo RL , Folkert W, Liebsch NJ, Chen YL , Pedlow FX , Schwab JH , Rosenberg AE , Nielsen GP , Szymonifka J, Ferreira AE, Hornicek FJ , DeLaney TF . (2015) J Neurosurg Spine. 2015 Dec;23(6):788-97.

[18F]-Fluoromisonidazole Positron Emission Tomography/Computed Tomography Visualization of Tumor Hypoxia in Patients With Chordoma of the Mobile and Sacrococcygeal Spine. Cheney MD, Chen YL, Lim R, Winrich BK, Grosu AL, Trofimov AV, Depauw N, Shih HA, Schwab JH, Hornicek FJ, DeLaney TF. Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1030-6.

Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Weyman EA, Yeap BY, Depauw N, Nielsen GP, Harmon DC, Yoon SS, Chen YL, Schwab JH, Hornicek FJ. J Surg Oncol. 2014 Aug;110(2):115-22.

Genotyping Cancer-Associated Genes in Chordoma Identifies Mutations in Oncogenes and Areas of Chromosomal Loss Involving CDKN2A, PTEN, and SMARCB1. Choy E, MacConaill LE, Cote GM, Le LP, Shen JK, Nielsen GP, Iafrate AJ, Garraway LA, Hornicek FJ, Duan Z. PLoS One. 2014 Jul 1;9(7)

Prognostic significance of miRNA-1 (miR-1) expression in patients with chordoma. Duan Z, Shen J, Yang X, Yang P, Osaka E, Choy E, Cote G, Harmon D, Zhang Y, Nielsen GP, Spentzos D, Mankin H, Hornicek F.J Orthop Res. 2014 May;32(5):695-701

Tissue microarray immunohistochemical detection of brachyury is not a prognostic indicator in chordoma. Zhang L, Guo S, Schwab JH, Nielsen GP, Choy E, Ye S, Zhang Z, Mankin H, Hornicek FJ, Duan Z.PLoS One. 2013 Sep 23;8(9)

Definitive High Dose Photon/Proton Radiotherapy for Unresected Mobile Spine and Sacral Chordomas. Chen YL, Liebsch N, Kobayashi W, Goldberg S, Kirsch D, Calkins G, Childs S, Schwab J, Hornicek F, Delaney T. Spine (Phila Pa 1976). 2013 Apr 19

Establishment and characterization of a novel chordoma cell line: CH22. Liu X, Nielsen GP, Rosenberg AE, Waterman PR, Yang W, Choy E, Sassi S, Yang S, Harmon DC, Yang C, Schwab JH, Kobayashi E, Mankin HJ, Xavier R, Weissleder R, Duan Z, Hornicek FJ. J Orthop Res. 2012 Apr 13. doi: 10.1002/jor.22113

Extended dermal apposition: a simple technique for the closure of irradiated perineal and sacral wounds. Hartzell TL, Medina M, Hornicek FJ, Austen WG Jr. Plast Reconstr Surg. 2011 Jun;127(6):170e-3e

Recurrent chromosomal copy number alterations in sporadic chordomas Le LP, Nielsen GP, Rosenberg AE, Thomas D, Batten JM, Deshpande V, Schwab J, Duan Z, Xavier RJ, Hornicek FJ, Iafrate AJ. PLoS One. 2011;6(5):e18846. Epub 2011 May 13

Nanoparticles: a promising modality in the treatment of sarcomas. Susa M, Milane L, Amiji MM, Hornicek FJ, Duan Z.Pharm Res. 2011 Feb;28(2):260-72. Epub 2010 May 27.

Proteomic profiling of chordoma. DeLaney TF, Duan Z, Hornicek FJ. J Surg Oncol. 2010 Dec 1;102(7):719. doi: 10.1002/jso.21766

Characterization and analysis of human chordoma cell lines Yang C, Hornicek FJ, Wood KB, Schwab JH, Choy E, Iafrate J, Rosenberg A, Nielsen GP, Xavier RJ, Mankin H, Duan Z. Spine 2010 Jun 1;35(13):1257-64

Blockage of Stat3 With CDDO-Me Inhibits Tumor Cell Growth in Chordoma Yang C, Hornicek FJ, Wood KB, Schwab JH, Choy E, Mankin H, Duan Z. Spine 2010 Apr 9. [Epub ahead of print]PMID: 20386502 [PubMed - as supplied by publisher]

Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in met expression
Duan Z, Choy E, Nielsen G, Rosenberg A, Iafrate J, Yang C, Schwab J, Mankin H, Xavier R, Hornicek F. Journal of Orthopedic Research 2009 Dec 29

Sacral Chordoma
Farsad K, Kattapuram SV, Sacknoff R, Ono J, Nielsen GP. Radiographics. 29(5):1525-30, 2009 Sep-Oct.

A novel target for treatment of chordoma: signal transducers and activators of transcription 3 Yang C, Schwab JH, Schoenfeld AJ, Hornicek FJ, Wood KB, Nielsen GP, Choy E, Mankin H, Duan Z. Mol Cancer Ther 2009 Sep;8(9):2597-605.

Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Schwab J, Antonescu C, Boland P, Healey J, Rosenberg A, Nielsen P, Iafrate J, Delaney T, Yoon S, Choy E, Harmon D, Raskin K, Yang C, Mankin H, Springfield D, Hornicek F, Duan Z. Anticancer Res. 2009 Jun;29(6):1867-71. PMID: 19528441 [PubMed - in process]

Aberrant hyperactivation of akt and Mammalian target of rapamycin complex 1 signaling in sporadic chordomas. Han S, Polizzano C, Nielsen GP, Hornicek FJ, Rosenberg AE, Ramesh V. Clin Cancer Res. 2009 Mar 15;15(6):1940-6. Epub 2009 Mar 10. PMID: 19276265

Combination short-course preoperative irradiation, surgical resection, and reduced-field high-dose postoperative irradiation in the treatment of tumors involving the bone. Wagner TD, Kobayashi W, Dean S, Goldberg SI, Kirsch DG, Suit HD, Hornicek FJ, Pedlow FX, Raskin KA, Springfield DS, Yoon SS, Gebhardt MC, Mankin HJ, Delaney TF. Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):259-66. PMID: 19100921

Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas.
DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Dean S, Yeap BY, McManus P, Rosenberg AE, Nielsen GP, Harmon DC, Spiro IJ, Raskin KA, Suit HD, Yoon SS, Hornicek FJ. Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):732-9. Epub 2008 Dec 25. PMID: 19095372

Chordoma and chondrosarcoma gene profile: implications for immunotherapy. Schwab JH, Boland PJ, Agaram NP, Socci ND, Guo T, O'Toole GC, Wang X, Ostroumov E, Hunter CJ, Block JA, Doty S, Ferrone S, Healey JH, Antonescu CR. Cancer Immunol Immunother. 2009 Mar;58(3):339-49. Epub 2008 Jul 19.
PMID: 18641983

The surgical pathology of notochordal remnants in adult intervertebral disks: a report of 3 cases.
Wang WL, Abramson JH, Ganguly A, Rosenberg AE. Am J Surg Pathol. 2008 Aug;32(8):1123-9. PMID: 18545146

Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De Maglio G, den Bakker MA, Di Francesco L, Kalil RK, Athanasou NA, O'Donnell P, McCarthy EF, Flanagan AM. Am J Surg Pathol. 2008 Apr;32(4):572-80. PMID: 18301055

Intraosseous benign notochord cell tumors (BNCT): further evidence supporting a relationship to chordoma. Deshpande V, Nielsen GP, Rosenthal DI, Rosenberg AE. Am J Surg Pathol. 2007 Oct;31(10):1573-7. PMID: 17895760

Clonality studies in sacral chordoma. Klingler L, Trammell R, Allan DG, Butler MG, Schwartz HS. Cancer Genet Cytogenet. 2006 Nov;171(1):68-71. PMID: 17074594

Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases.
Hoch BL, Nielsen GP, Liebsch NJ, Rosenberg AE. Am J Surg Pathol. 2006 Jul;30(7):811-8. PMID: 16819322

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor. Park L, Delaney TF, Liebsch NJ, Hornicek FJ, Goldberg S, Mankin H, Rosenberg AE, Rosenthal DI, Suit HD. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1514-21. Epub 2006 Jun 6. PMID: 16757128

Sarcoma and skin radiation oncology. Nedea EA, DeLaney TF. Hematol Oncol Clin North Am. 2006 Apr;20(2):401-29. Review. PMID: 16730300

Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs). Yang XR, Beerman M, Bergen AW, Parry DM, Sheridan E, Liebsch NJ, Kelley MJ, Chanock S, Goldstein AM. Int J Cancer. 2005 Sep 1;116(3):487-91. PMID: 15818627

Spinal cord tolerance to high-dose fractionated 3D conformal proton-photon irradiation as evaluated by equivalent uniform dose and dose volume histogram analysis. Marucci L, Niemierko A, Liebsch NJ, Aboubaker F, Liu MC, Munzenrider JE. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):551-5. PMID: 15145175

Anterior spinal arthrodesis with structural cortical allografts and instrumentation for spine tumor surgery.Lewandrowski KU, Hecht AC, DeLaney TF, Chapman PA, Hornicek FJ, Pedlow FX. Spine (Phila Pa 1976). 2004 May 15;29(10):1150-8; discussion 1159. Review. PMID: 15131446

Clinical outcome in chordoma: utility of flow cytometry in DNA determination. Berven S, Zurakowski D, Mankin HJ, Gebhardt MC, Springfield DS, Hornicek FJ. Spine (Phila Pa 1976). 2002 Feb 15;27(4):374-9. PMID: 11840103

Chordoma periphericum: a case report. Nielsen GP, Mangham DC, Grimer RJ, Rosenberg AE. Am J Surg Pathol. 2001 Feb;25(2):263-7. PMID: 11176077

Role of onlay grafting with minimal internal fixation for occipitocervical fusion in oncologic patients. Sanpakit S, Mansfield TL, Liebsch J. J Spinal Disord. 2000 Oct;13(5):382-90. PMID: 11052346

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