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MOLECULAR CARACTERISATION OF SOFT TISSUE SARCOMAS WITH COMPLEX GENETICS Frédéric Chibon Pauline Lagarde - Jean-Michel Coindre - Alain Aurias Tumor Genetics.

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Presentation on theme: "MOLECULAR CARACTERISATION OF SOFT TISSUE SARCOMAS WITH COMPLEX GENETICS Frédéric Chibon Pauline Lagarde - Jean-Michel Coindre - Alain Aurias Tumor Genetics."— Presentation transcript:

1 MOLECULAR CARACTERISATION OF SOFT TISSUE SARCOMAS WITH COMPLEX GENETICS Frédéric Chibon Pauline Lagarde - Jean-Michel Coindre - Alain Aurias Tumor Genetics Département of Pathology Insititut Bergonie – Bordeaux - FRANCE

2 GENETIC CLASSIFICATION OF STS Sarcomas with recurrent translocations Sarcomas with oncogenic mutations Sarcomas with simple genetics Sarcomas with a complex genetic profile

3 SARCOMAS WITH A COMPLEX GENETIC PROFILE Leiomyosarcomas Adult Rhabdomyosarcomas Pleomorphic Liposarcomas Myxofibrosarcomas Poorly-differentiated sarcomas / MFH

4 SARCOMAS WITH A COMPLEX GENETIC PROFILE Different prognosis but…. … Difficult to classify ! share similar morphology Share histological patterns with dedifferentiated liposarcomas Genetic mechanisms still poorly understood

5 French Sarcoma Group Database 2538 adult STS with untreated primary tumor: (January 2006) Well differentiated and dedifferentiated LPS: 262 (10.3%) LMS, adult RMS, pleomorphic LPS, MFS and Poorly-Differentiated Sarcomas (PDS) / MFH: 1183 (46.6%)

6 Analyzed tumors: CGH ARRAY: 203 cDNA ARRAY: 170 LPS DD 30% LMS 35% MFH-PDS 35% COMPLEX GENETIC PROFIL OF SOFT TISSUE SARCOMAS MFH 50% MFS 25% PDS 25%

7 DD LPS LMS MFH + PDS Two main subgroups of genetic profiles AmplificationGainLoss

8 DD LPS: Simple Genetics based on co-amplifications AmplificationGainLoss MDM2 is amplified without CDK4 in 10% of the tumors Simple and specific genetics: 10 /40 were misdiagnosed DD LPS LMS MFH

9 Two different profils correspond to two different types of LMS LIMBLIMB TRUNKTRUNK E xt I nt 10q23 13q14 10q13q141q23-qter 17p12 17p13 5p 16q12 -q22 7p AmplificationGainLoss Average rearrangement number: 37 Average rearrangement number: 26 LIMB TRUNK

10 Identification of a target gene Non Amplified tumors Amplified tumors 23 Mb CGH ARRAYcDNA ARRAY Identification of driver genes in amplifications Chr 5 PDS / MFHLMSDD LPS

11 5p p=0,08 Overall Survival Time in months probability Normal or loss Amplification or gain 5p p=0,04 Overall Survival MFH Time in months probability Normal or loss Amplification or gain 5p Amplification : One gene amplified, up-regulated.......Wich effect on the tumor biology ? Genetic alterations and clinical datas 5p p=0,08 Metastasis Time in months probability Normal or loss Amplification or gain

12 CONCLUSION Scientific project based on a virtual tumor bank with all clinical, pathological, biological criterias and follow up Identification of genomic alterations and target genes 1q21-q24 5p 7p 10q 13q 17p CGH: a really helpfull tool in STS diagnosis At least TWO distinct LMS Complementarity of CGH and cDNA arrays Diagnosis Prognosis Therapeutic target MFH / PDS with « LMS alterations » have to be reviewed by pathologist

13 MOLECULAR CARACTERISATION OF STS WITH COMPLEX GENETICS Alain Aurias Caroline Louis Jean-Michel Coindre Binh Nguyen Bui Pauline Lagarde Véronique Brouste Cécile Garcia 11 CLCC French Sarcoma Group Pathologist


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