Establishment of a Prospective Clinical-biological Database (BCBSarcome)

A Clinical and Biological Database will provide to the scientific community a collection of blood and tissues with clinical data to improve knowledge about cancer and help to develope new cancer treatments. This database is specific to Sarcoma

Liposarcomas (LPS) are soft tissue tumours of mesenchymal origin. The most common histological subtypes, represented by well differenciated Lipsarcomas (WD-LPS) and dedifferenciated (DD-LPS), are characterized by the quasi-systematic amplification of the q13-15 of chromosome 12 containing the Mdm2 gene. The systematic amplification of the Mdm2 gene is such that it is used clinically to distinguish WD/DD-LPS from other types of sarcomas. These observations raise key questions about the high selection pressure that leads to the almost systematic amplification of Mdm2 during the development of these LPS. Mdm2 is an oncoprotein whose roles in p53 tumour suppressor degradation are broadly described. However, the different inhibitors targeting this interaction were disappointing in clinical trials. Recently a team from the U1194 INSERM unit of the IRCM which collaborates in this project showed by a pan-genomics analysis, that Mdm2 is recruited to chromatin within a multiproteic complex having as target a transcriptional program involved in the metabolism and in particular in the biosynthesis of the serin. This clinical-biological basis will allow the continuation of this research project on liposarcomas and the development of new research projects on other histological types of sarcomas.

For all the patients include in the study : Paraffin tissue samples collected during surgery (neoplasic tissue and normal tissue) MDM2 project : Blood samples collected at different times : Before the surgery, and 1 month after the surgery circulant DNA project : Blood samples collected at different times : Before the surgery, and 1 month after the surgery radiotherapy toxicity : Blood samples collected before the radiotherapy In parallel to this biological collection, standardized clinical data will be entered into a database

MDM2 project : Blood samples collected at different times : Before the surgery, and 1 month after the surgery circulant DNA project : Blood samples collected at different times : Before the surgery, and 1 month after the surgery radiotherapy toxicity : Blood samples collected before the radiotherapy

Establishment a clinical and biological database will provide to the scientific community a collection of blood and tissues with clinical data to improve knowledge about sarcoma

number of collection of tissue samples (tumour tissue and healthy tissue) in patients operated on a sarcoma associated with clinical data.

Establishment a clinical and biological database will provide to the scientific community a collection of blood and tissues with clinical data to improve knowledge about sarcoma

Inclusion Criteria: men or women > 18 years Patient treated by surgery for : a primitive sarcoma and/or local relapse sarcoma and/or metastatic localisation of sarcoma patient accepted blood sample patient treated by radiotherapy before or after the surgery Patient signed informed consent Exclusion Criteria: Patient not affiliated to french Social Protection system Patient under guardianship Patient unable to understand or comply with study instructions or requirements for psychological, family, social or geographical reasons Pregnancy and/or feeding Patient take care in an Emergency Situation

Ducimetiere F, Lurkin A, Ranchere-Vince D, Decouvelaere AV, Peoc'h M, Istier L, Chalabreysse P, Muller C, Alberti L, Bringuier PP, Scoazec JY, Schott AM, Bergeron C, Cellier D, Blay JY, Ray-Coquard I. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One. 2011;6(8):e20294. doi: 10.1371/journal.pone.0020294. Epub 2011 Aug 3.

Mastrangelo G, Coindre JM, Ducimetiere F, Dei Tos AP, Fadda E, Blay JY, Buja A, Fedeli U, Cegolon L, Frasson A, Ranchere-Vince D, Montesco C, Ray-Coquard I, Rossi CR. Incidence of soft tissue sarcoma and beyond: a population-based prospective study in 3 European regions. Cancer. 2012 Nov 1;118(21):5339-48. doi: 10.1002/cncr.27555. Epub 2012 Apr 19.

Crago AM, Singer S. Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma. Curr Opin Oncol. 2011 Jul;23(4):373-8. doi: 10.1097/CCO.0b013e32834796e6.

Lokka S, Scheel AH, Dango S, Schmitz K, Hesterberg R, Ruschoff J, Schildhaus HU. Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a report of two cases. BMC Clin Pathol. 2014 Jul 28;14:36. doi: 10.1186/1472-6890-14-36. eCollection 2014.

Marine JC, Lozano G. Mdm2-mediated ubiquitylation: p53 and beyond. Cell Death Differ. 2010 Jan;17(1):93-102. doi: 10.1038/cdd.2009.68.

Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, Heil F, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT, Nichols GL, Bui BN. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol. 2012 Nov;13(11):1133-40. doi: 10.1016/S1470-2045(12)70474-6. Epub 2012 Oct 17.