1 / 12

J. Fernebro, P. Francis , P. Edén, Å. Borg, I. Panagopoulos,

Gene expression profiles relate to gene fusion type and metastasis in synovial sarcoma. J. Fernebro, P. Francis , P. Edén, Å. Borg, I. Panagopoulos, F. Mertens, J. Vallon-Christersson, M. Åkerman, N. Mandahl, M. Nilbert

lance-kaufman
Download Presentation

J. Fernebro, P. Francis , P. Edén, Å. Borg, I. Panagopoulos,

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Gene expression profiles relate to gene fusion type and metastasis in synovial sarcoma J. Fernebro, P. Francis, P. Edén, Å. Borg, I. Panagopoulos, F. Mertens, J. Vallon-Christersson, M. Åkerman, N. Mandahl, M. Nilbert Departments of Oncology, Theoretical Physics, Clinical Genetics, and Pathology Lund University, Sweden Princy.Francis@onk.lu.se

  2. Aims • Groups of genes discriminating the monophasic from biphasic • have been previously identified • (Allander et al., 2002; Nagayama et al., 2002) • Do gene expression profiles in synovial sarcoma correlate with: • Histopathology • Cytogenetics • Gene fusion type • Metastatic potential

  3. Material SS18 SSX 23 synovial sarcoma specimens from 21 patients mean age 46, 12 males, 16 primary tumors, 3 local recurrences, 4 metastases • Histopathologymonophasic (17)vs biphasic (4) • Cytogenetics t(X;18) (4)vs complex karyotype (12) • Gene fusion type SS18/SSX1 (12) vsSS18/SSX2 (7) • Metastatic potential metastasis (13)vs metastsis-free (5)

  4. Methods Tumour RNA Reference RNA Labelled cDNA Hybridize to microarray slide 18-20 hrs incubation at 42oC Scan Image and Data Analysis Process Image • cDNA microarray, 27648 IMAGE clones • distinct reporters • 17517 unique UniGene clusters • Hierarchical clustering • based on ~5800 genes • - Unsupervised • - Supervised • Golub scores, random permutation tests

  5. Supervised clustering • Metastasis • No • Yes • Gene fusion type • Type 1 • Type 2 • Expression profiles did not relate to histopathology or karyotype • Significant discriminators for gene fusion type and metastatic potential

  6. Discriminating genes Gene fusion type Metastatic potential Up SS18/SSX1 • - TCF7 - LEF1 • - RTP801 - CKB • - NOTCH2 - Metallothioneins Up metastasis • - TYMS - TOP2A • - PTTG1 - IGFBP2 • - BUB1 - COL18A1 Up SS18/SSX2 • - BENE - MN1 • - NEDD4 - FRAG1 • MSX2 - TIEG Up without metastasis • - ProSAPiP1 - TNNT1 • - ICAM1 - DDX21 • - FRAG1 - TCF8 • Cell proliferation • Cell cycle progression • Transcriptional regulation • Transcription factors • Signalling molecules • Multiple metallothioneins

  7. Discriminating genes Gene fusion type Metastatic potential Up SS18/SSX1 • - TCF7 - LEF1 • - RTP801 - CKB • - NOTCH2 - Metallothioneins Up metastasis • - TYMS - TOP2A • - PTTG1 - IGFBP2 • - BUB1 - COL18A1 Up SS18/SSX2 • - BENE - MN1 • - NEDD4 - FRAG1 • MSX2 - TIEG Up without metastasis • - ProSAPiP1 - TNNT1 • - ICAM1 - DDX21 • - FRAG1 - TCF8 Common discriminators • BSG - FRAG1 • NOTCH2 - RGS2 • - TCF7 - TCF8 • 45 from top 200 common to both lists • Up in metastasis also up in SS18/SSX1

  8. Discriminating genes Gene fusion type Metastatic potential Up SS18/SSX1 • - TCF7 - LEF1 • - RTP801 - CKB • - NOTCH2 - Metallothioneins Up metastasis • - TYMS - TOP2A • - PTTG1 - IGFBP2 • - BUB1 - COL18A1 Up SS18/SSX2 • - BENE - MN1 • - NEDD4 - FRAG1 • MSX2 - TIEG Up without metastasis • - ProSAPiP1 - TNNT1 • - ICAM1 - DDX21 • - FRAG1 - TCF8 Targets for chemotherapeutic drugs

  9. Discriminating genes Gene fusion type Metastatic potential Up SS18/SSX1 • - TCF7 - LEF1 • - RTP801 - CKB • - NOTCH2 - Metallothioneins Up metastasis • - TYMS - TOP2A • - PTTG1 - IGFBP2 • - BUB1 - COL18A1 Up SS18/SSX2 • - BENE - MN1 • - NEDD4 - FRAG1 • MSX2 - TIEG Up without metastasis • - ProSAPiP1 - TNNT1 • - ICAM1 - DDX21 • - FRAG1 - TCF8 Previously reported in synovial sarcoma

  10. Discriminating genes Gene fusion type Metastatic potential Up SS18/SSX1 • - TCF7 - LEF1 • - RTP801 - CKB • - NOTCH2 - Metallothioneins Up metastasis • - TYMS - TOP2A • - PTTG1 - IGFBP2 • - BUB1 - COL18A1 Up SS18/SSX2 • - BENE - MN1 • - NEDD4 - FRAG1 • MSX2 - TIEG Up without metastasis • - ProSAPiP1 - TNNT1 • - ICAM1 - DDX21 • - FRAG1 - TCF8 Previously reported in metastasizing tumors

  11. Conclusions • Differentially expressed genes relative to gene fusion type and metastatic potential in synovial sarcoma • Signaling molecules, transcription factors and metallothioneins among the fusion type discriminating genes • Known targets for chemotherapy (TYMS and TOP2A) upregulated in metastasizing tumors

More Related