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Presentation

Clinical Research Group  « Genetics of solid tumors  »


Pr Florence PEDEUTOUR, PU-PH1, Team Leader


Summary


The Laboratory of Solid Tumor Genetics was created in 2004 in the context of launch of the first the National Plan Against Cancer. The goal of this creation was to develop a translational activity in the field of genetics of solid tumors.

We are involved both in a clinical activity (affiliation: Nice University Hospital (CHU de Nice) and in a research program (affiliation: IRCAN). Our two main research interests are focused on genetics of soft tissue tumors and renal cell carcinomas, respectively. In addition, we closely interact with the French National Cancer Institute (INCa), the Cancéropôle Provence-Alpes-Côte d’Azur and the French Sarcoma Group (GSF-GETO). We also have a teaching and tutorial activity in oncology and genetics at the Faculty of Medicine of Nice as well as in national courses.


CLINICAL ACTIVITY IN SOMATIC CANCER GENETICS

The 28 French regional platforms were created in 2006 on the behalf of INCa in order to provide molecular tests for diagnosis and for predictive response to personalized targeted drugs (http://www.e-cancer.fr/soins/plates-formes-hospitalieres-de-genetique-moleculaire). Our clinical laboratory belongs to the Platform of Molecular Genetics of Cancers of the eastern part of Provence-Alpes-Côte d’Azur (PACA-est) region (six laboratories including ours; regional coordinator: F. Pedeutour).


Cytogenetic and molecular diagnosis

We provide a comprehensive test panel for diagnosis and evaluation of solid tumors, such as pediatric tumors, tumors of soft tissues and bones, brain tumors, skin tumors or renal tumors. We perform cytogenetic and molecular analyses as complementary tools of histopathological diagnosis, in collaboration with pathologists, surgeons and oncologists. We receive each year more than a thousand fresh, frozen or fixed-paraffin-embedded samples for chromosomal or molecular analyses. Depending on the indication and nature of the biological samples, we do cytogenetic analysis including preparation of karyotypes, metaphase and interphase based fluorescence in situ hybridization (FISH), comparative genomic hybridization based array (CGH array) as well as molecular analysis including mutation detection by RT-PCR, pyrosequencing, real time PCR or Sanger sequencing. The detection of somatic chromosomal alterations such as genomic amplification, translocations, fusion genes, deletions or DNA sequence anomalies such as nucleotide mutations is a powerful ancillary tool for diagnosis of solid tumors and therapeutic management. It helps the distinction between benign and malignant tumors and the recognition of a variety of malignant tumor types or subtypes. In particular, we are expert in the field of molecular diagnoses in sarcomas. Chromosomal analyses are also helpful for evaluation of prognosis (a typical example is the detection of MYCN amplification in neuroblastomas or genomic profiles in choroid melanomas).


 Fig 1 :

 Fig 2 :

 Predictive molecular tests

A part of our clinical activity consists in detection of DNA mutations that are predictive of response or non-response to targeted therapies, such as tyrosine kinase inhibitors or monoclonal antibodies. The main current indications are mutations of KRAS, BRAF, EGFR, ALK, HER2, KIT and PDGFRA in colon cancers, lung cancers, melanomas and stromal gastro-intestinal tumors (GIST).


Fig 3 :

 

CLINICAL RESEARCH PROJECTS

Our research projects are closely related to our clinical activity. We aim: -1) to identify novel chromosomal and genetic anomalies in order to improve classification and diagnosis of solid tumors and -2) to explore the functional consequences of these novel anomalies.


Our current research projects are mainly dedicated to :

Molecular rearrangements and dysregulation of HMGA2 in adipose tissue tumors

Adipose tissue tumors are the most frequent human tumors. They are mainly represented by lipomas that are very common benign lesions. The malignant adipose tumors include three main subtypes, well-differentiated and dedifferentiated liposarcomas, myxoid and round cell liposarcomas and pleomorphic liposarcomas. The current challenges for improving the surgical and therapeutic management of adipose tumors are identification of novel diagnostic and prognostic markers  as well as of therapeutic targets.


Strikingly, it can be noted the high frequency of rearrangements of chromosome 12 long arm (12q). Indeed, chromosomal anomalies in lipomas mainly involve structural balanced and non-balanced alterations of chromosome 12 long arm in the region of HMGA2 (12q14.3) whereas amplification of the 12q14-15 region including MDM2 is the hallmark of well-differentiated/dedifferentiated liposarcomas and rearrangements of DDIT3 (12q13.3) are characteristic of myxoid liposarcomas. We have shown that HMGA2 is rearranged not only in lipomas but is also recurrently amplified in well-differentiated/dedifferentiated liposarcomas (Italiano et al., 2008 and 2009). We also recently reported the first observation of overexpression of HMGA2 in a unique case of lipomatosis (Saada et al., 2012). We therefore hypothesize that HMGA2 is a key gene in adipose lesions and tumors. We have shown that HMGA2 overexpression in lipomas is not always associated to chromosome 12q anomalies and is not significantly correlated to inhibition of let7 miRNA expression (Bianchini et al., 2011). Our aim is to understand the complex mechanisms of dysregulation of HMGA2 and how these alterations contribute to adipose tissue pathogenesis.


Genomic characterization of renal cell carcinomas

Renal cell carcinomas (RCC) account for approximately 10 500 novel cases/year in France and are responsible of the death of 4000 patients/year. The last World Health Organization (WHO) classification describes ten types of RCC, the most frequent of which are clear cell RCC followed by papillary RCC and chromophobe RCC. A precise and reliable histopathological typing of RCC is crucial since survival and response to treatment is variable from one type to another. Notably, since 2006 treatment of clear cell RCC has dramatically benefited from the use of targeted antiangiogenic molecules. However diagnosis of RCC is often difficult and approximately 15% of cases remain “unclassified”. Though some correlations between histology and genetics have been well established (for instance, deletion of VHL gene at 3p25 in clear cell RCC, trisomy 7 and 17 in papillary RCC or hypodiploidy in chromophobe RCC), programs of exploration of genomic and molecular profiles of RCC are necessary to improve our knowledge of these tumors. To note, a particular subtype, RCC with Xp11 translocation and rearrangement of TFE3 has been individualized thanks to chromosomal studies.


Since 2005 we have established a collaboration with the departments of Urology (PR Amiel) and the central laboratory of pathology (Pr Michiels) of Nice university hospital. We have karyotyped all RCC operated in the urology department (50/year). We have extended the chromosomal analyses by combining additional immunohistochemistry, FISH and array-CGH analysies. We have focused our research on two types of morphologically challenging RCC: RCC with Xp11 translocation and type 2-papillary RCC. Our aim is to use genomic tools to provide a better characterization of unclassified and rare subtypes of RCC.

Research Projects

Research Projects


Research Project 1

"Genomic and functional characterization of adipose tissue tumors"


Liposarcomas are the most common type of soft tissue sarcomas (STS) and among them well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) are the most frequent.  WDLPS are composed mostly of mature fat whereas DDLPS contain two cell components in variable proportions: a WDLPS component and a non lipogenic sarcoma component of variable histological grade. More than 50% of DDLPS will relapse locally, a significant proportion of patients will remain with non-resectable disease. 1- Clinical and histological diagnosis of these tumors can be difficult. 2- Metastases occur in about 20% of DDLPS. Standard chemotherapy is poorly efficient and alternative options are so far limited underscoring the urgent need to identify new therapeutic targets.


Our aim is to characterize molecular features of liposarcoma in order to identify diagnostic markers and relevant therapeutic targets.


We have previously established several important features of WDLPS/DDLPS (see references below) and are currently interested in the following research projects :



1 - Role of the lipid phosphate phosphatases (LPP) in adipogenesis and adipose tissue tumorigenesis


We have already shown that HMGA2 plays an important role in adipose tissue tumorigenesis. We have recently identified the lipid phosphate phosphatase PPAP2B as a novel recurrent translocation partner of HMGA2 in lipomas. Using the hMADS (human Multipotent Adipose-Derived Stem) cells as a model of human adipocyte differentiation we are investigating the role of the LPP in adipogenesis (Collaboration with the teams of C. Dani and EZ. Amri Institut Biologie Valrose (IBV), Nice).


We have also determined the expression profiles of the LPP in WDLPS and DDLPS and we are performing functional studies on the WDLPS cell lines that we have established in the lab to determine whether LPP play a role in liposarcomagenesis.



2 - Role of the SDC1/FGF/FGFR signalling pathway in liposarcoma tumorigenesis


Our preliminary results (in collaboration with C. Dani’s team, IBV Nice) suggest that syndecan-1 (SDC1) might be involved in DDLPS tumorigenesis. We plan to analyse :


- The pattern of expression and localisation of syndecans, FGFs and FGFRs in WDLPS/DDLPS both in a large collection of primary tumors and on WDLPS /DDLPS cell lines.

- The prognostic value of SDC1 and FGF expression by correlation to the patient clinical outcomes

- The effects of modulating SDC1, FGFR expression in WDLPS and DDLPS cells on cell proliferation, cell cycle, apoptosis and on their capacity to differentiate in adipocytes.


References


1. Italiano A., Bianchini L., Keslair F., Bonnafous S., Cardot N., Coindre JM., Dumollard JM., Hofman P., Leroux A., Mainguené C., Peyrottes I., Ranchere-Vince D., Tran A., Gual P., Pedeutour F. HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinct inconsistent amplicon. Int. J. Cancer, 2008, 122 : 2233-2241.


2. Italiano A., Bianchini L.,Gjernes E., Keslair F., Ranchere-Vince D., Dumollard JM., Haudebourg J., Leroux A.,  Mainguené C., Terrier P., Chibon F., Coindre JM., Pedeutour F. Clinical and biological significance of CDK4 amplification in well-differentiated and dedifferentiated liposarcomas. Clin. Cancer Res., 2009, 15 : 5696-5703.


3. Bianchini L., Saada E., Gjernes E., Marty M., Haudebourg J., Birtwisle-Peyrottes I., Keslair F., Chignon-Sicard B., Chamorey E., Pedeutour F. Let-7 microRNA and HMGA2 levels of expression are not inversely linked in adipocytic tumors: analysis of 56 lipomas and liposarcomas. Genes Chromosomes Cancer, 2011, 50 : 442-455.


4. Wagner KD., Benchetrit M., Bianchini L., Michiels JF., Wagner N. Peroxisome Proliferator-Activated Receptor Beta/Delta (PPARa/d) is highly expressed in liposarcoma and promotes migration and proliferation. J Pathol., 2011, 224 : 575-588.


5. Saada E., Bianchini L, Mouroux J., Dupré F., Butori C ;, Birtwisle-Peyrottes I., Padovani B., Yver M., Ferrari C., Pedeutour F. First description of inhibition of let-7 microRNA expression and HMGA2 overexpression in a case of deep-seated diffuse lipomatosis. Histopathology, 2012, 61: 519-522.


6. Pedeutour F., Maire G., Pierron A., Thomas DM, Garsed DW., Bianchini L, Duranton-Tanneur V., Cortes-Maurel A., Italiano A., Squire J., Coindre JM. A newly characterized human well-differentiated liposarcoma cell line contains amplification of the 12q12-21 and 10p11-14 regions. Virchows Arch., 2012, 461: 67-78.


7. Bianchini L., Birtwisle L., Saada E., Bazin A., Long E., Roussel JF., Michiels JF., Forest F., Dani C., Myklebost O., Birtwisle-Peyrottes I., Pedeutour F. Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas. Genes Chromosomes Cancer, 2013, 52: 580-590.


Research Project 2

" Identification of novel genetic markers in renal tumors "



Diagnosis and treatment of renal cancer : a major issue


The management of renal cell carcinoma (RCC) is a major health issue. Both the incidence of metastatic disease at the time of initial diagnosis and the rate of mortality are high.  The diagnosis of RCC is based on morphological, immunohistochemical and genetic features. The classification of the World Health Organization (WHO) lists ten types of renal cell tumors.  Clear cell RCC (ccRCC) and papillary RCC (pRCC) are the most frequent types. Genetic analysis of RCC is of great diagnostic use and helps for understanding the pathogenesis of these tumors. The therapeutic management of patients has been improved by genetic data in ccRCC. Indeed, it is well established that the VHL gene is inactivated  in ccRCC. This inactivation results in tumor angiogenesis through the HIF/VEGF pathway and is the basis of the development of anti-angiogenic therapies to treat metastatic disease. We believe that the genetic characterization of pRCC might result in assessment of personalized treatments.  pRCC classically show a gain of chromosomes 7 and 17 and loss of the Y chromosome (Figure 1). Moreover, approximately 10% of sporadic pRCC present mutations in the MET gene (Figure 2).




Figure 1 :
Characteristic quantitative genomic profile of a papillary renal cell carcinoma showing a gain of
chromosome 7 and 17 and a loss of chromosome Y (▼), additional anomalies are also present (▼).

.
.

Figure 2 :
Reverse-direction sequencing of the exon 16 of the MET gene. A point mutation c.3334C>T ; p.His1112Tyr (*) is observed. Mutations within exons 14 to 19 of MET are observed in approximately 13% of papillary renal cell carcinoma of type 1.



Our strengths


Since 2005, in collaboration with the Department of Urology (Pr Amiel) and the Central Laboratory of Pathology (Pr Michiels), renal tumors operated at the University Hospital of Nice have been systematically studied by molecular cytogenetic methods. We also established a collaboration with the Department of Pathology of Princess Grace Hospital in Monaco (Dr Dupré). Our approach combines comparative genomic hybridization on microarray (array-CGH), fluorescence in situ hybridization (FISH), conventional karyotyping and targeted sequencing. In collaboration with the genomic platform of IRCAN (team leader G. Cristofari), we also integrate targeted high-throughput sequencing.


Objectives


Our aim is to identify new genetic markers of renal tumors, useful for diagnosis and treatment. We are particularly interested in "unclassified" tumors such as tumor combining several types of RCC (1,2,3,4) or challenging diagnosis tumors such as pRCC type 2. We hypothesize that the entity pRCC of type 2 is actually a heterogeneous group of tumors. Some pRCC type 2 derive from pRCC type 1 while some may correspond to distinct origin. In addition, some rare benign renal tumors can be difficult to diagnose correctly and would benefit from a better genetic characterization. This is the case of metanephric adenomas (4). We are also interested in studying genetic factors of predisposition  to RCC (5).


References and publications


(1) Haudebourg J, Hoch B, Fabas T, Burel-Vandenbos F, Carpentier X, Amiel J, Cardot-Leccia N, Michiels JF, Pedeutour F. A novel case of t(X;1)(p11.2;p34) in a renal cell carcinoma with TFE3 rearrangement and favorable outcome in a 57-year-old patient. Cancer Genet Cytogenet. 2010;200(2):75‑78.


(2) Haudebourg J, Hoch B, Fabas T, Cardot-Leccia N, Burel-Vandenbos F, Vieillefond A, Amiel J, Michiels JF, Pedeutour F. Strength of molecular cytogenetic analyses for adjusting the diagnosis of renal cell carcinomas with both clear cells and papillary features: a study of three cases. Virchows Arch. 2010;457(3):397‑404.


(3) Calderaro J, Moroch J, Pierron G, Pedeutour F, Maillé P, Soyeux P, de la Taille A, Couturier J, Vieillefond A, Rousselet MC, Delattre O, Allory Y. SMARCB1/INI1 inactivation in renal medullary carcinoma, Histopathology, 2012, 61:428-35.


(4) Dadone B, Ambrosetti D, Carpentier X, Duranton-Tanneur V, Burel-Vandenbos F, Amiel J, Pedeutour F. A renal metanephric adenoma showing both a 2p16-24 deletion and a BRAF V600E mutation: a synergistic role for a tumor suppressor gene on chromosome 2p and BRAF activation ? Cancer Genet., 2013, 206 (9-10) : 347-52.


(5) Doyen J, Carpentier X, Haudebourg J, Hoch B, Karmous-Benailly H, Ambrosetti D, Fabas T, Amiel J, Lambert JC, Pedeutour F. Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer. Cancer Genet. 2012;205(11):603‑607.

(6) Grepin R, Ambrosetti D, Marsaud A, Gastaud L, Amiel J, Pedeutour F, Pagès G.  The relevance of testing the efficacy of anti-angiogenesis treatments on cells derived from primary tumors : a new method for the personalized treatment of renal cell carcinoma. PlosOne, 2014, Mar27;9(3):e89449.



Research Group

Research Group




 (photo 2015)



PEDEUTOUR Florence, PU-PH1, Oncology & Genetics, Group Leader
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Research Team IRCAN :

BIANCHINI Laurence, CR1 CNRS
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GRATTERY Roger, TCS CNRS
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NGOMAI Mélanie, M2R UNS
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KOSTHOWA Ludovic, M2 INSERM
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Hospital Team (Hospital Center of Nice) :

AMIEL Jean, PH-PHCE
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BAZIN Audrey, Technician CHU
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DADONE Bérengère, CCA
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DELHORBE Mickaël, Technician CHU
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DI MAURO Ilaria, ARC
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DURAND Matthieu, PH
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DURANTON-TANNEUR Valérie, Biology-Engineer
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FABAS Thibault, Technician CHU
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GIMET Sophie, Technician CHU
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KESLAIR Frédérique, Technician CHU
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KUBINIEK Valérie, PH
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PEDEUTOUR-BRACCINI Zoé, CCA
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PEYRON Annie-Claude, Technician CHU
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SALLENAVE Julie, Technician CHU
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(March 2016)


Press Articles

Le Fil de l'UNS (University of Nice)


Régional Newspaper "Nice-Matin", October 10th, 2015

"Rares Cancers : patients, researchers, hand in hand"



Rewards


Pr Florence PEDEUTOUR et Drs Laurence BIANCHINI et Bérangère DADONE


On June 25th, 2015, during the annual meeting of the French Sarcoma Group in Bordeaux,

Laurence Bianchini and Florence Pedeutour received a price from the "Info-Sarcomes Association"

(President Mrs Estelle Lecointe) for their research project : 

"La voie de signalisation cellulaire FGF/FGFR : une nouvelle cible thérapeutique dans

les liposarcomes dédifférencés".


All informations are available on  http://www.infosarcomes.org/projets-de-lannee-2015.



Publications

Publications



2016


Burel-Vandenbos F, Ngo-Mai M, Dadone B, Di Mauro I, Gimet S, Saada-Bouzid E, Bourg V, Almairac F, Fontaine D,

Virolle T, Pedeutour F.

MET immunolabeling is a useful predictive tool for MET gene amplification in glioblastoma.

Neuropathol Appl Neurobiol., 2016, Mar 4.


Dequeker EM, Keppens C, Egele C, Delen S, Lamy A, Lemoine A, Sabourin JC, Andrieu C, Ligtenberg M, Fetique D, Tops B,

Descarpentries C, Blons H, Denoux Y, Aube C, Penault-Llorca F, Hofman P, Leroy K, Le Marechal C, Doucet L, Duranton-Tanneur V,

Pedeutour F, Soubeyran I, Côté JF, Emile JF, Vignaud JM, Monhoven N, Haddad V, Laurent-Puig P, van Krieken H, Nowak F,

Lonchamp E, Bellocq JP, Rouleau E.

Three Rounds of External Quality Assessment in France to Evaluate the Performance of 28 Platforms for Multiparametric

Molecular Testing in Metastatic Colorectal and Non-Small Cell Lung Cancer.

J Mol Diagn., 2016, Mar;18(2):205-14.


2015


Zaragosi LE, Dadone B, Michiels JF, Marty M, Pedeutour F, Dani C, Bianchini L.

Syndecan-1 regulates adipogenesis: new insights in dedifferentiated liposarcoma tumorigenesis.

Carcinogenesis, 2015, Jan;36(1):32-40.


Karanian M, Pérot G, Coindre JM, Chibon F, Pedeutour F, Neuville A.

Fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans.

Mod Pathol., 2015, Feb;28(2):230-7.


Doyen J, Duranton-Tanneur V, Hostein I, Karanian-Philippe M, Chevreau C, Breibach F, Coutts M, Dadone B, Saint-Paul MC,

Gugenheim J, Duffaud F, Pedeutour F.

Spatio-temporal genetic heterogeneity of CTNNB1 mutations in sporadic desmoid type fibromatosis lesions.

Virchows Arch., 2015, Dec 14.


Saâda-Bouzid E, Burel-Vandenbos F, Ranchère-Vince D, Birtwisle-Peyrottes I, Chetaille B, Bouvier C, Château MC, Peoc'h M,

Battistella M, Bazin A, Gal J, Michiels JF, Coindre JM, Pedeutour F, Bianchini L.

Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas.

Mod Pathol., 2015, Nov;28(11):1404-14.


Dadone B, Refae S, Lemarié-Delaunay C, Bianchini L, Pedeutour F.

Molecular cytogenetics of pediatric adipocytic tumors.

Cancer Genet., 2015, Oct;208(10):469-81.


Sievers E, Trautmann M, Kindler D, Huss S, Gruenewald I, Dirksen U, Renner M, Mechtersheimer G, Pedeutour F,

Åman P, Nishio J, Schildhaus HU, Kirfel J, Schirmacher P, Wardelmann E, Buettner R, Hartmann W.

SRC inhibition represents a potential therapeutic strategy in liposarcoma.

Int J Cancer, 2015, Dec 1;137(11):2578-88.


Marsaud A, Dadone B, Ambrosetti D, Baudoin C, Chamorey E, Rouleau E, Lefol C, Roussel JF, Fabas T, Cristofari G,

Carpentier X, Michiels JF, Amiel J, Pedeutour F.

Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several

independent diseases.

Genes Chromosomes Cancer, 2015, Jun;54(6):369-82.



2014


Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L, Schröder J, Li J, Feng ZP, Kim BW, Kowarsky M, Lansdell B,

Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KH, Damore MA, Deans AJ, Papenfuss AT, Thomas DM.

The architecture and evolution of cancer neochromosomes.

Cancer Cell., 2014, Nov10;26(5):653-67.


Grépin R, Ambrosetti D, Marsaud A, Gastaud L, Amiel J, Pedeutour F, Pagès G.

The relevance of testing the efficacy of anti-angiogenesis treatments on cells derived from primary tumors:

a new method for the personalized treatment of renal cell carcinoma.

PLoS One, 2014, Mar27;9(3):e89449.


2013


Dadone B, Ambrosetti D, Carpentier X, Duranton-Tanneur V, Burel-Vandenbos F, Amiel J, Pedeutour F.

A renal metanephric adenoma showing both a 2p16e24 deletion and BRAF V600E mutation: a synergistic role for a

tumor suppressor gene on chromosome 2p and BRAF activation ?

Cancer Genet., 2013, Sep-Oct;206(9-10):347-52.


Baffert S, Italiano A, Pierron G, Traoré MA, Rapp J, Escande F, Ghnassia JP, Terrier P, Voegeli AC, Ranchere-Vince D,

Coindre JM, Pedeutour F.

Comparative cost analysis of molecular biology methods in the diagnosis of sarcomas.

Bull Cancer, 2013, Oct;100(10):963-71.


Villalva C, Duranton-Tanneur V, Guilloteau K, Burel-Vandenbos F, Wager M, Doyen J, Levillain PM, Fontaine D, Blons H,

Pedeutour F, Karayan-Tapon L.

EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients.

Cancer Med., 2013, Jun;2(3):296-304.


Natale R, Thariat J, Vedrine PO, Bozec A, Peyrottes I, Marcy PY, Haudebourg J, Pedeutour F, Saâda E, Thyss A.

Conservative multimodal management of a primitive neuroectodermal tumor of the thyroid.

Rare Tumors, 2013, May29;5(2):75-8.


Belaid A, Cerezo M, Chargui A, Corcelle-Termeau E, Pedeutour F, Giuliano S, Ilie M, Rubera I, Tauc M, Barale S, Bertolotto C,

Brest P, Vouret-Craviari V, Klionsky DJ, Carle GF, Hofman P, Mograbi B.

Autophagy plays a critical role in the degradation of active RHOA, the control of cell cytokinesis, and genomic stability.

Cancer Res., 2013, Jul15;73(14):4311-22.


Bianchini L, Birtwisle L, Saâda E, Bazin A, Long E, Roussel JF, Michiels JF, Forest F, Dani C, Myklebost O, Birtwisle-Peyrottes I,

Pedeutour F.

Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas.

Genes Chromosomes Cancer, 2013, Jun;52(6):580-90.


Harnet JC, Pedeutour F, Raybaud H, Ambrosetti D, Fabas T, Lombardi T.

Immunohistological features in adenomatoid odontogenic tumor: review of the literature and first expression and

mutational analysis of β-catenin in this unusual lesion of the jaws.

J Oral Maxillofac Surg., 2013, Apr;71(4):706-13.


Burel-Vandenbos F, Ambrosetti D, Coutts M, Pedeutour F. 

EGFR mutation status in brain metastases of non-small cell lung carcinoma.

J Neurooncol., 2013, Jan 111(1):1-10.


Bertucci F, Bouvier-Labit C, Finetti P, Adélaïde J, Metellus P, Mokhtari K, Decouvelaere AV, Miquel C, Jouvet A,
Figarella-Branger D, Pedeutour F, Chaffanet M, Birnbaum D. 
Comprehensive genome characterization of solitary fibrous tumors using high-resolution array-based
comparative genomic hybridization.
Genes Chromosomes Cancer, 2013, Feb 52(2):156-64.


2012



Doyen J, Carpentier X, Haudebourg J, Hoch B, Karmous-Benailly H, Ambrosetti D, Fabas T, Amiel J,
Lambert JC, Pedeutour F.
Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link
between the constitutional t(11;22) and cancer.
Cancer Genet. 2012 , Nov 205(11):603-7.

Calderaro J, Moroch J, Pierron G, Pedeutour F, Grison C, Maillé P, Soyeux P, de la Taille A, Couturier J,
Vieillefond A, Rousselet MC, Delattre O, Allory Y.
SMARCB1/INI1 inactivation in renal medullary carcinoma.
Histopathology, 2012, Sept. 61 (3), 428-435.

Pedeutour F, Maire G, Pierron A, Thomas DM, Garsed DW, Bianchini L, Duranton-Tanneur V, Cortes-Maurel A,
Italiano A, Squire JA, Coindre JM.
A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21
and 10p11-14 regions.
Virchows Arch. 2012 Jul;461(1):67-78.

Saâda E, Bianchini L, Mouroux J, Dupré F, Butori C, Birtwisle-Peyrottes I, Padovani B, Yver M, Ferrari C,
Pedeutour F.
First description of inhibition of let-7 microRNA expression and HMGA2 overexpression in a case of deep-seated
diffuse lipomatosis.
Histopathology, 2012 Sep 61(3):519-22.   

Pedeutour F, Deville A, Steyaert H, Ranchere-Vince D, Ambrosetti D, Sirvent N.
Rearrangement of HMGA2 in a case of infantile lipoblastoma without PLAG1 alteration.
Pediatr Blood Cancer, 2012 May 58(5):798-800.  

Darini CY, Pisani DF, Hofman P, Pedeutour F, Sudaka I, Chomienne C, Dani C, Ladoux A.
Self-renewal gene tracking to identify tumour-initiating cells associated with metastatic potential.
Oncogene, 2012, May 10;31(19):2438-49.
  

2011

Wagner KD, Benchetrit M, Bianchini L, Michiels JF, Wagner N.
Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is highly expressed in liposarcoma and promotes
migration and proliferation.
J Pathol. 2011 Aug;224(4):575-88

Italiano A, Michalak S, Soulié P, Peyron AC, Pedeutour F.
Trisomy 6p and ring chromosome 11 in a melanotic schwannoma suggest relation to malignant melanoma
rather than conventional schwannoma.
Acta Neuropathologica, 2011 May 121(5):669-70.  

Bianchini L, Saâda E, Gjernes E, Marty M, Haudebourg J, Birtwisle-Peyrottes I, Keslair F, Chignon-Sicard B,
Chamorey E, Pedeutour F.
Let-7 microRNA and HMGA2 levels of expression are not inversely linked in adipocytic tumors: analysis of
56 lipomas and liposarcomas with molecular cytogenetic data.
Genes Chromosomes Cancer, 2011 Jun 50: (6):442-55.   

Dujardin F, Binh MB, Bouvier C, Gomez-Brouchet A, Larousserie F, Muret AD, Louis-Brennetot C, Aurias A, Coindre JM,
Guillou L, Pedeutour F, Duval H, Collin C, de Pinieux G.
MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other
primary fibro-osseous lesions of the bone.
Mod Pathol. 2011, May 24(5):624-37.

Leclerc-Mercier S, Pedeutour F, Fabas T, Glorion C, Brousse N, Fraitag S.
A potentially misleading case of a Plexiform Fibro-Histiocytic Tumor in a child with molecular and cytogenetic analysis.
Pediatric Dermatol, 2011, 28: 26-29.

Stacchiotti S, Pedeutour F, Negri T, Conca E, Marrari A, Palassini E, Collini P, Keslair F, Morosi C, Gronchi A, Pilotti S, Casali PG.
Dermatofibrosarcoma protuberans-derived fibrosarcoma: Clinical history, biological profile and sensitivity to imatinib.
Int J Cancer, 2011, 129 : 1761-1772.

Saâda E, Peoc'h M, Decouvelaere AV, Collard O, Peyron AC, Pedeutour F.
CCND1 and MET genomic amplification during malignant transformation of a giant cell tumor of bone.
J Clin Oncol, 2011, 29:86-9.

Watkin E, Devouassoux-Shisheboran M, Pedeutour F, Lagarde P, Salle M, Ranchère-Vince D, Baulieux J, Barnoud R.
A First Reported Case of Dedifferentiated Liposarcoma of the Esophagus with Molecular Diagnosis.
J Gastrointest Cancer, 2011, 42 :65-67.



2010

Sabatier R, Bouvier C, de Pinieux G, Sarran A, Brenot-Rossi I, Pedeutour F, Chetaille B, Viens P, Weiller PJ, Bertucci F.
Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature.
BMC Cancer. 10:645, 2010. (IF : 3,087)

Haudebourg J, Hoch B, Fabas T, Burel-Vandenbos F, Carpentier X, Amiel J, Cardot-Leccia N, Michiels JF, Pedeutour F
A novel case of variant translocation t(X;1)(p11.2;p34) in a renal cell carcinoma with TFE3 rearrangement and
favorable outcome in a 57-year-old patient.
Cancer Genet Cytogenet, 200: 75-78, 2010. (IF : 1,482)

Haudebourg J, Hoch B, Fabas T, Cardot-Leccia N, Burel-Vandenbos F, Vieillefond A, Amiel J, Michiels JF, Pedeutour F.
Strength of Molecular Cytogenetic Analyses for Adjusting the Diagnosis of Renal Cell Carcinomas with Both Clear Cells
and Papillary Features: a Study of Three Cases. Virchows Arch, 457: 397-404, 2010. (IF : 2, 082)

Buche S, Delasalle EM, Coindre JM, Pedeutour F, Kolb F, Staumont-Salle D, Mortier L.
Atypical presentation of giant cell fibroblastoma.
Ann Dermatol Venereol. 2010 May;137(5):381-5. French.

Kérob D, Porcher R, Vérola O, Dalle S, Maubec E, Aubin F, D’Incan M, Bodokh I, Boulinguez S, Madelaine-Chambrin I,
Mathieu- Boué A, Servant JM, de Kerviler E, Janin A, Calvo F, Pedeutour F, Lebbé C.
Imatinib mesylate (IM) as a pre-operative therapy in dermatofibrosarcoma : results of a multicentric phase II study on 25 patients.
Clin Cancer Res, 16:3288-3295, 2010. (IF : 6,488)

Italiano A, Hostein I, Soubeyran I, Fabas T, Benchimol D, Evrard S, Gugenheim J, Becouarn Y, Brunet R, Fonck M, François E,
Saint-Paul MC, Pedeutour F.
KRAS and BRAF Mutational Status in Primary Colorectal Tumors and Related Metastatic Sites: Biological and Clinical Implications.
Ann Surg Oncol, 17: 1429-1434, 2010. (IF: 3,898)

Giacchero D, Maire G, Nuin P.A.S, Berthier F, Ebran N, Carlotti A, Celerier P, Coindre J. M, Esteve E, Fraitag S, Guillot B,
Ranchere-Vince D, Saiag P, Terrier P, Lacour J.P, Pedeutour F.
No correlation between the molecular subtype of COL1A1-PDGFB fusion gene and the clinico-histopathological features of
dermatofibrosarcoma protuberans.
J Invest Dermatol, 130:904-907, 2010. (IF : 5.251).

2009


Pierron A, Fernandez C, Saada E, Keslair F, Hery G, Zattara H, Pedeutour F.
HMGA2-NFIB fusion in a pediatric intramuscular lipoma: a novel case of NFIB alteration in a large deep-seated adipocytic tumor.
Cancer Genet Cytogenet, 2009, 195 : 66-70. (IF : 1,482)

Sirvent N, Trassard M, Ebran N, Attias R, Pedeutour F.
Fusion of EWS with the DUX4/Fascioscapulohumeral muscular dystrophy region resulting from a (4;22)(q35;q12) in a case of
embryonal rhabdomyosarcoma.
Cancer Genet Cytogenet, 2009, 195 :12-18. (IF : 1,482)

Italiano A, Bianchini L, Gjernes E, Keslair F, Ranchere-Vince D, Dumollard JM, Haudebourg J, Leroux A, Mainguené C, Terrier P,
Chibon F, Coindre JM, Pedeutour F.
Clinical and Biological Significance of CDK4 Amplification in Well-Differentiated and Dedifferentiated Liposarcomas.
Clin Cancer Res, 5: 5696-703, 2009. (IF : 6,488)

Coindre JM, Pedeutour F, Aurias A.
Well-differentiated and dedifferentiated liposarcomas.
Virchows Arch. 2010 Feb;456(2):167-79. Epub 2009 Aug 18. Review

Italiano A, Cortot AB, Ilie M, Martel-Planche G, Fabas T, Pop D, Mouroux J, Hofman V, Hofman P, Pedeutour F.
EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: implications for anti-EGFR treatment of a rare
lung malignancy
Int J Cancer, 125:2479-82, 2009. (IF : 4,734)

Pires de Camargo V, van de Rijn M, Maestro R, de Alava E, Madoz-Gúrpide J, Pilotti S, von Mehren M, Pedeutour F, Maki RG,
Rutkowski P, Thomas DM.
Other targetable sarcomas.
Semin Oncol. 2009 Aug;36(4):358-71

Hélias-Rodzewicz Z, Pedeutour F, Coindre JM, Terrier P, Aurias A.
Selective Elimination of Amplified CDK4 Sequences Correlates with Spontaneous Adipocytic Differentiation in Liposarcoma.
Genes Chromosomes Cancer, 48:943-952, 2009. (IF : 3,925)

Bidault F, Vanel D, Terrier P, Jalaguier A, Bonvalot S, Pedeutour F, Couturier JM, Dromain C.
Liposarcoma or lipoma: Does genetics change classic imaging criteria?
Eur J Radiol. 72 :22-26, 2009

Ilie M, Hofman V, Pedeutour F, Attias R, Santini J, Hofman P.
Oncocytic lipoadenoma of the parotid gland: Immunohistochemical and cytogenetic analysis.
Pathol Res Pract. 2010 Jan 15;206(1):66-72. Epub 2009 Apr 5.10.

Raoux D, Péoc'h M, Pedeutour F, Vaunois B, Decouvelaere AV, Folpe AL.
Primary epithelioid sarcoma of bone: report of a unique case, with immunohistochemical and fluorescent in situ hybridization
confirmation of INI1 deletion.
Am J Surg Pathol. 2009 Jun;33(6):954-8.

Marque M, Bessis D, Pedeutour F, Viseux V, Guillot B, Fraitag-Spinner S.
Medallion-like dermal dendrocyte hamartoma: the main diagnostic pitfall is congenital atrophic dermatofibrosarcoma.
Br J Dermatol. 2009 Jan;160(1):

Italiano A, Maire G, Sirvent N, Nuin P.A.S, Keslair F, Foa C, Louis C, Aurias A, Pedeutour F.
Variability of Origin for the Neocentromeric Sequences in Analphoid Supernumerary Marker Chromosomes of Well-Differentiated
Liposarcomas.
Cancer Letters, 273:323-30, 2009. (IF : 3,504).

2008

Italiano A, Ebran N, Attias R, Chevallier A, Monticelli I, Mainguené C, Benchimol D, Pedeutour F.
NFIB Rearrangement in Superficial, Retroperitoneal and Colonic Lipomas with Chromosome 9p22 Aberrations.
Genes Chromosomes Cancer, 47:971-977, 2008. (IF : 3,925)

Cardot-Leccia N, Italiano A, Haudebourg J, Attias R, Amato D, Pedeutour F, Perrin C.
Cutaneous myxolipoma with apocrine glandular differentiation: description of a new clinico-pathological variant with
chromosome 6p21 rearrangement,
Histopathology, 53:361-363, 2008. (IF : 4,131)

Italiano A, Chambonniere M-L, Attias R, Chibon F, Coindre J-M, Pedeutour F.
Monosomy 7 and absence of 12q amplification in two cases of spindle cell liposarcomas.
Cancer Genet Cytogenet, 184:99-10, 2008. (IF : 1,482)

Rouzier C, Soler C, Hofman P, Brennetot C, Bieth E, Pedeutour F.
Ovarian dysgerminoma and Apert syndrom.
Pediatric Blood Cancer, 50:696-8, 2008. (IF : 2,394)

Rouzier C, Haudebourg J, Carpentier X, Valério L, Amiel J, Michiels JF, Pedeutour F.
Detection of the TMPRSS2-ETS fusion gene in prostate carcinomas: retrospective analysis of 55 formalin-fixed and
paraffin embedded samples with clinical data.
Cancer Genet Cytogenet, 183: 21-27, 2008. (IF : 1,482)

Kerob D, Pedeutour F, Leboeuf C, Verola O, de Kerviler E, Servant JM, Sarandi F, Bousquet G, Madelaine-Chambrin I,
Pruvost C, Calvo F, Janin A, Lebbe C.
Value of cytogenetic analysis in the treatment of dermatofibrosarcoma protuberans.
J Clin Oncol, 26:1757-9, 2008. (IF : 17,157)

Surace C, Pedeutour F, Trombetta D, Burel-Vandenbos F, Rocchi M, Storlazzi CT.
MYCN is uncommonly amplified in the form of episomes in a case of medulloblastoma.
Virchows Arch, 452:491-7, 2008. (IF : 2, 082)

Bianchini L, Maire G, Guillot B, Joujoux JM, Follana P, Simon MP, Coindre JM, Pedeutour F.
Complex t(5;8) involving the CSPG2 and PTK2B genes in a Case of Dermatofibrosarcoma Protuberans without the
COL1A1-PDGFB Fusion.
Virchows Arch, 452:689-96, 2008. (IF : 2, 082)

Italiano A, Bianchini L, Keslair F, Bonnafous S, Cardot-Leccia N, Coindre JM, Dumollard JM, Hofman P, Leroux A,
Mainguené C, Peyrottes I, Ranchere-Vince D, Terrier P, Tran A, Gual P, Pedeutour F.
HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a
distinct inconsistent amplicon.
Int J Cancer. 2008 May 15;122(10):2233-41.

Benchetrit M, Hofman V, Long E, Odin G, Basc E, Pasquier B, Pedeutour F, Hofman P.
Primary Clear Cell Meningioma of the Orbit Mimicking a Metastatic Carcinoma. Usefulness of Immunohistochemistry and
Cytogenetic Analysis.
Virchows Arch, 2008, 452:209-13. (IF : 2, 082)

Italiano A, Follana P, Caroli FX, Badetti JL, Benchimol D, Garnier G, Gugenheim J, Haudebourg J, Keslaier F, Lesbats G,
Lledo G, Roussel JF, Pedeutour F, François E.
Cetuximab shows activity in colorectal patients with tumors for which FISH analysis does not detect an increase in EGFR
gene copy number.
Annals of Surgical Oncology, 15:649-54, 2008. (IF : 3,898).


2007

Benchetrit M, Hofman V, Venissac N, Italiano A, Aurias A, Brennetot C, Pedeutour F, Hofman P.
Dedifferentiated liposarcoma of the pleura mimicking a malignant solitary fibrous tumor and associated with dedifferentiated
liposarcoma of the mediastinum. Usefulness of cytogenetic and molecular genetics analyses.
Cancer Genet Cytogenetics, 2007, 179 : 150-155.

Sirvent N, Coindre JM, Maire G, Hostein I, Keslair F, Guillou L, Ranchere-Vince D, Terrier P, Pedeutour F.
Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples:
utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR.
Am J Surg Pathol, 31:1476-1489, 2007.

Guillou L, Benhattar J, Gengler C, Gallagher G, Ranchere-Vince D, Collin F, Terrier P, Leroux A, Marquès B,
de Saint-Aubain-Sommerhausen N, Keslair F, Pedeutour F, Coindre J-M.
Translocation-positive low grade fibromyxoid sarcoma : clinicopathologic and molecular analysis of a series expanding
the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma. A study from the french sarcoma group.
Am J Surg Pathol, 31:1387-1402, 2007.

Jouary T, Beltran C, Coindre JM, Plagnol P, Taieb A, Ebran N, Pedeutour F, Delaunay M.
Dermatofibrosarcoma protuberans occurring in two brothers : role of environmental or genetic factors ?
J Am Acad Dermatol, 57:S58-60, 2007.

Italiano A, Cardot N, Dupré F, Monticelli I, Keslair F, Piche M, Mainguené C, Coindre JM, Pedeutour F.
Gains and Complex Rearrangements of the 12q13-15 Chromosomal Region in Ordinary Lipomas: the “Missing Link”
Between Lipomas and Liposarcomas?
Int J Cancer, 121: 308-315, 2007. (IF : 4,555)

Müller CR, Paulsen E, Noordhuis P, Pedeutour F, Sæter G, Vassilev LT, Myklebost O.
Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A.
Int J Cancer, 121: 199-205, 2007. (IF : 4,555)

Bianchini L, Maire G, Pedeutour F; Groupe Francophone de Cytogénétique Oncologique.
From cytogenetics to cytogenomics of dermatofibrosarcoma protuberans family of tumors.
Bull Cancer. 2007 Feb;94(2):179-89.

Maire G, Fraitag S, Galmiche L, Keslair F, Ebran N, Terrier-Lacombe MJ, de Prost Y, Pedeutour F.
A clinical, histologic, and molecular study of 9 cases of congenital dermatofibrosarcoma protuberans.
Arch Dermatol. 2007 Feb;143(2):203-10.

Cardot-Leccia N, Italiano A, Monteil MC, Basc E, Perrin C, Pedeutour F.
Naevus lipomatosus superficialis: a case report with a deletion 2p24.
Br J Dermatol, 156:380-381, 2007. (IF : 3,489).


2006

Craver R, Dewenter T, Ebran N, Pedeutour F.
COL1A1-PDGFB fusion in a pediatric Bednar tumor with 2 copies of der(17;22),
Cancer Genet Cytogenet,168: 155-157, 2006.

Harik LR, Merino C, Coindre JM, Amin MB, Pedeutour F, Weiss SW.
Pseudosarcomatous Myofibroblastic Proliferations of the Bladder. A Clinicopathologic Study of 42 Cases.
Am J Surg Pathol, 30 :787-794, 2006.

Hieronimus S, Bec-Roche M, Pedeutour F, Lambert J-C, Wagner-Mahler K, Mas J-C, Sadoul J-L, Fénichel P.
The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11.
Eur J Endocrinology, 155 :47-52, 2006.

Butori C, Hofman V, Attias R, Mouroux J, Pedeutour F, Hofman P.
Diagnosis of Primary Esophageal Synovial Sarcoma by Demonstration of t(X;18) Translocation. A Case Report.
Virchows Arch, 449:262-7, 2006.

Italiano A, Attias R, Aurias A, Pérot G, Burel-Vandenbos F, Otto J, Venissac N, Pedeutour F.
Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 Neocentromere and
9p23-24 amplification including JAK2 and JMJD2C.
Cancer Genet Cytogenet, 167:122-130, 2006.

Kostrzewa E, Beylot-Barry M, Vergier B, Pedeutour F, Beylot C.
Childhood-onset multifocal atrophic dermatofibrosarcoma.
Ann Dermatol Venereol. 2006 Apr;133(4):359-61.

Italiano A, Burel Vandenbos F, OttoJ, Mouroux J, Fontaine D, Marcy P-Y, Cardot N, Thyss A Pedeutour F.
Comparison of Epidermal Growth Factor Receptor Gene and Protein in Primary Non-Small-Cell-Lung Cancer and
Metastatic Sites: Implications for Treatment with EGFR-Inhibitors.
Annals of Oncology, 17:981-5, 2006.


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