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

7. Two main subgroups of genetic profiles
DD LPS
LMS
MFH +
PDS
Amplification
Gain
Loss

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

9. Two different profils correspond to two different types of LMS
10q23
13q14
10q
1q23-qter
17p12
17p13 5p
16q12
-q22 7p
LIMB
Average rearrangement number: 37
Average rearrangement number: 26
LIMB
TRUNK
TRUNK
Ext
Int
Amplification
Gain
Loss

10. Identification of driver genes in amplifications
CGH ARRAY
cDNA ARRAY
Identification of a target gene
Non
Amplified tumors
Amplified
tumors
23 Mb
Chr 5
PDS / MFH
LMS
DD LPS

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

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

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