Étude de la valeur diagnostique et pronostique d'un profil d'expression génique par la technique de RT‐MLPA dans les lymphomes à cellules du manteau

HAL Id: dumas-00908885

https://dumas.ccsd.cnrs.fr/dumas-00908885

Submitted on 25 Nov 2013

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RT-MLPA dans les lymphomes à cellules du manteau

Ophélie Cassuto

To cite this version:

Ophélie Cassuto. Étude de la valeur diagnostique et pronostique d’un profil d’expression génique par la technique de RT-MLPA dans les lymphomes à cellules du manteau. Médecine humaine et pathologie. 2013. �dumas-00908885�

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---

DOYEN : Professeur Pierre FREGER

ASSESSEURS : Professeur Michel GUERBET

Professeur Benoit VEBER Professeur Pascal JOLY Professeur Bernard PROUST

DOYENS HONORAIRES : Professeurs J. BORDE – Ph. LAURET – H. PIGUET – C. THUILLEZ

PROFESSEURS HONORAIRES : MM. M-P AUGUSTIN – J. ANDRIEU-GUITRANCOURT – M. BENOZIO -

J. BORDE – Ph. BRASSEUR – R. COLIN – E. COMOY – J. DALION – S. DESHAYES – C. FESSARD – J.P. FILLASTRE – P. FRIGOT – J. GARNIER – J. HEMET – B. HILLEMAND – G. HUMBERT – J.M. JOUANY – R. LAUMONIER – Ph. LAURET – M. LE FUR – J.P. LEMERCIER – J.P. LEMOINE – M. MAGARD – B. MAITROT – M. MAISONNET – F. MATRAY – P. MITROFANOFF – A.M. ORECCHIONI – P. PASQUIS – H. PIGUET – M. SAMSON – M. SAMSON-DOLLFUS – J.C. SCHRUB – R. SOYER – B. TARDIF-TESTART – J.M. THOMINE – C. THUILLEZ – P. TRON – C. WINCKLER – L.M. WOLF

I - MEDECINE

PROFESSEURS

M. Frédéric ANSELME HCN Cardiologie

Mme Isabelle AUQUIT AUCKBUR HCN Chirurgie Plastique

M. Bruno BACHY HCN Chirurgie pédiatrique

M. Fabrice BAUER HCN Cardiologie

Mme Soumeya BEKRI HCN Biochimie et Biologie Moléculaire

M. Jacques BENICHOU HCN Biostatistiques et informatique médicale

M. Jean-Paul BESSOU HCN Chirurgie thoracique et cardio-vasculaire

Mme Françoise BEURET-BLANQUART CRMPR Médecine physique et de réadaptation

M. Guy BONMARCHAND HCN Réanimation médicale

M. Olivier BOYER UFR Immunologie

M. Jean-François CAILLARD (Surnombre) HCN Médecine et santé au Travail

M. François CARON HCN Maladies infectieuses et tropicales

M. Philippe CHASSAGNE HB Médecine interne (Gériatrie)

M. Vincent COMPERE HCN Anesthésiologie et réanimation chirurgicale M. Alain CRIBIER (Surnombre) HCN Cardiologie

M. Jean - Nicolas DACHER HCN Radiologie et Imagerie Médicale

M. Stéfan DARMONI HCN Informatique Médicale/Techniques de communication

M. Pierre DECHELOTTE HCN Nutrition

Mme Danièle DEHESDIN HCN Oto-Rhino-Laryngologie

M. Jean DOUCET HB Thérapeutique/Médecine – Interne - Gériatrie.

M. Bernard DUBRAY CB Radiothérapie

M. Philippe DUCROTTE HCN Hépato – Gastro - Entérologie

M. Frank DUJARDIN HCN Chirurgie Orthopédique - Traumatologique

M. Fabrice DUPARC HCN Anatomie - Chirurgie Orthopédique et Traumatologique

M. Bertrand DUREUIL HCN Anesthésiologie et réanimation chirurgicale

Mle Hélène ELTCHANINOFF HCN Cardiologie

M. Thierry FREBOURG UFR Génétique

M. Pierre FREGER HCN Anatomie/Neurochirurgie

M. Jean François GEHANNO HCN Médecine et Santé au Travail

M. Emmanuel GERARDIN HCN Imagerie Médicale

Mme Priscille GERARDIN HCN Pédopsychiatrie

M. Michel GODIN HB Néphrologie

M. Philippe GRISE HCN Urologie

M. Didier HANNEQUIN HCN Neurologie

M. Fabrice JARDIN CB Hématologie

M. Luc-Marie JOLY HCN Médecine d’urgence

M. Pascal JOLY HCN Dermato - vénéréologie

M. Jean-Marc KUHN HB Endocrinologie et maladies métaboliques

Mme Annie LAQUERRIERE HCN Anatomie cytologie pathologiques

M. Vincent LAUDENBACH HCN Anesthésie et réanimation chirurgicale

M. Joël LECHEVALLIER HCN Chirurgie infantile

M. Hervé LEFEBVRE HB Endocrinologie et maladies métaboliques

M. Thierry LEQUERRE HB Rhumatologie

M. Eric LEREBOURS HCN Nutrition

Mle Anne-Marie LEROI HCN Physiologie

M. Hervé LEVESQUE HB Médecine interne

Mme Agnès LIARD-ZMUDA HCN Chirurgie Infantile

M. Pierre Yves LITZLER HCN Chirurgie Cardiaque

M. Bertrand MACE HCN Histologie, embryologie, cytogénétique

M. Eric MALLET (Surnombre) HCN Pédiatrie

M. Christophe MARGUET HCN Pédiatrie

Mle Isabelle MARIE HB Médecine Interne

Mme Véronique MERLE HCN Epidémiologie

M. Pierre MICHEL HCN Hépato - Gastro - Entérologie

M. Francis MICHOT HCN Chirurgie digestive

M. Bruno MIHOUT (Surnombre) HCN Neurologie

M. Jean-François MUIR HB Pneumologie

M. Marc MURAINE HCN Ophtalmologie

M. Philippe MUSETTE HCN Dermatologie - Vénéréologie

M. Christophe PEILLON HCN Chirurgie générale

M. Jean-Marc PERON HCN Stomatologie et chirurgie maxillo-faciale

M. Christian PFISTER HCN Urologie

M. Jean-Christophe PLANTIER HCN Bactériologie - Virologie

M. Didier PLISSONNIER HCN Chirurgie vasculaire

M. Bernard PROUST HCN Médecine légale

M. François PROUST HCN Neurochirurgie

Mme Nathalie RIVES HCN Biologie et méd. du dévelop. et de la reprod.

M. Jean-Christophe RICHARD (Mise en dispo) HCN Réanimation Médicale, Médecine d’urgence

M. Horace ROMAN HCN Gynécologie Obstétrique

M. Jean-Christophe SABOURIN HCN Anatomie – Pathologie

M. Guillaume SAVOYE HCN Hépato – Gastro

Mme Céline SAVOYE – COLLET HCN Imagerie Médicale

M. Michel SCOTTE HCN Chirurgie digestive

Mme Fabienne TAMION HCN Thérapeutique

Mle Florence THIBAUT HCN Psychiatrie d’adultes

M. Luc THIBERVILLE HCN Pneumologie

M. Christian THUILLEZ HB Pharmacologie

M. Hervé TILLY CB Hématologie et transfusion

M. François TRON (Surnombre) UFR Immunologie

M. Jean-Jacques TUECH HCN Chirurgie digestive

M. Jean-Pierre VANNIER HCN Pédiatrie génétique

M. Benoît VEBER HCN Anesthésiologie Réanimation chirurgicale

M. Pierre VERA C.B Biophysique et traitement de l’image

M. Eric VERIN CRMPR Médecine physique et de réadaptation

M. Eric VERSPYCK HCN Gynécologie obstétrique

M. Olivier VITTECOQ HB Rhumatologie

Mme Noëlle BARBIER-FREBOURG HCN Bactériologie – Virologie

M. Jeremy BELLIEN HCN Pharmacologie

Mme Carole BRASSE LAGNEL HCN Biochimie

Mme Mireille CASTANET HCN Pédiatrie

M. Gérard BUCHONNET HCN Hématologie

Mme Nathalie CHASTAN HCN Physiologie

Mme Sophie CLAEYSSENS HCN Biochimie et biologie moléculaire

M. Moïse COEFFIER HCN Nutrition

M. Manuel ETIENNE HCN Maladies infectieuses et tropicales

M. Guillaume GOURCEROL HCN Physiologie

Mme Catherine HAAS-HUBSCHER HCN Anesthésie - Réanimation chirurgicale

M. Serge JACQUOT UFR Immunologie

M. Joël LADNER HCN Epidémiologie, économie de la santé

M. Jean-Baptiste LATOUCHE UFR Biologie Cellulaire

Mme Lucie MARECHAL-GUYANT HCN Neurologie

M. Thomas MOUREZ HCN Bactériologie

M. Jean-François MENARD HCN Biophysique

Mme Muriel QUILLARD HCN Biochimie et Biologie moléculaire

M. Vincent RICHARD UFR Pharmacologie

M. Francis ROUSSEL HCN Histologie, embryologie, cytogénétique

Mme Pascale SAUGIER-VEBER HCN Génétique

Mme Anne-Claire TOBENAS-DUJARDIN HCN Anatomie

PROFESSEUR AGREGE OU CERTIFIE

Mme Dominique LANIEZ UFR Anglais

Mme Cristina BADULESCU UFR Communication

II - PHARMACIE

PROFESSEURS

M. Thierry BESSON Chimie Thérapeutique

M. Jean-Jacques BONNET Pharmacologie

M. Roland CAPRON (PU-PH) Biophysique

M. Jean COSTENTIN (Professeur émérite) Pharmacologie

Mme Isabelle DUBUS Biochimie

M. Olivier LAFONT Chimie organique

Mme Isabelle LEROUX Physiologie

M. Paul MULDER Sciences du médicament

Mme Martine PESTEL-CARON (PU-PH) Microbiologie

Mme Elisabeth SEGUIN Pharmacognosie

M Jean-Marie VAUGEOIS Pharmacologie

M. Philippe VERITE Chimie analytique

MAITRES DE CONFERENCES

Mle Cécile BARBOT Chimie Générale et Minérale

Mme Dominique BOUCHER Pharmacologie

M. Frédéric BOUNOURE Pharmacie Galénique

M. Abdeslam CHAGRAOUI Physiologie

M. Jean CHASTANG Biomathématiques

Mme Marie Catherine CONCE-CHEMTOB Législation pharmaceutique et économie de la santé

Mme Elizabeth CHOSSON Botanique

Mle Cécile CORBIERE Biochimie

M. Eric DITTMAR Biophysique

Mme Nathalie DOURMAP Pharmacologie

Mle Isabelle DUBUC Pharmacologie

Mme Roseline DUCLOS Pharmacie Galénique

M. Abdelhakim ELOMRI Pharmacognosie

M. François ESTOUR Chimie Organique

M. Gilles GARGALA (MCU-PH) Parasitologie

Mme Najla GHARBI Chimie analytique

Mle Marie-Laure GROULT Botanique

M. Hervé HUE Biophysique et Mathématiques

Mme Laetitia LE GOFF Parasitologie Immunologie

Mme Hong LU Biologie

Mme Sabine MENAGER Chimie organique

Mme Christelle MONTEIL Toxicologie

M. Mohamed SKIBA Pharmacie Galénique

Mme Malika SKIBA Pharmacie Galénique

Mme Christine THARASSE Chimie thérapeutique

M. Rémi VARIN (MCU-PH) Pharmacie Hospitalière

Mme Sandrine PANCHOU Pharmacie Officinale

PROFESSEUR CONTRACTUEL

Mme Elizabeth DE PAOLIS Anglais

ATTACHE TEMPORAIRE D’ENSEIGNEMENT ET DE RECHERCHE

M. Mazim MEKAOUI Chimie Analytique

Mlle Virginie OXARAN Microbiologie

M. Romy RAZAKANDRAINIBE Parasitologie

III – MEDECINE GENERALE

PROFESSEURS

M. Jean-Loup HERMIL UFR Médecine générale

PROFESSEURS ASSOCIES A MI-TEMPS :

M. Pierre FAINSILBER UFR Médecine générale

M. Alain MERCIER UFR Médecine générale

M. Philippe NGUYEN THANH UFR Médecine générale

MAITRE DE CONFERENCES ASSOCIE A MI-TEMPS :

M Emmanuel LEFEBVRE UFR Médecine générale

Mme Elisabeth MAUVIARD UFR Médecine générale

Mme Marie Thérèse THUEUX UFR Médecine générale

Melle Cécile BARBOT Chimie Générale et Minérale

M. Thierry BESSON Chimie thérapeutique

M. Roland CAPRON Biophysique

M Jean CHASTANG Mathématiques

Mme Marie-Catherine CONCE-CHEMTOB Législation, Economie de la Santé

Mle Elisabeth CHOSSON Botanique

M. Jean-Jacques BONNET Pharmacodynamie

Mme Isabelle DUBUS Biochimie

M. Loïc FAVENNEC Parasitologie

M. Michel GUERBET Toxicologie

M. Olivier LAFONT Chimie organique

Mme Isabelle LEROUX-NICOLLET Physiologie

Mme Martine PESTEL-CARON Microbiologie

Mme Elisabeth SEGUIN Pharmacognosie

M. Mohamed SKIBA Pharmacie Galénique

MAITRES DE CONFERENCES

M. Sahil ADRIOUCH Biochimie et biologie moléculaire (Unité Inserm 905)

Mme Gaëlle BOUGEARD-DENOYELLE Biochimie et biologie moléculaire (UMR 1079)

Mme Carine CLEREN Neurosciences (Néovasc)

Mme Pascaline GAILDRAT Génétique moléculaire humaine (UMR 1079)

M. Antoine OUVRARD-PASCAUD Physiologie (Unité Inserm 1096)

Mme Isabelle TOURNIER Biochimie (UMR 1079)

PROFESSEURS DES UNIVERSITES

M. Serguei FETISSOV Physiologie (Groupe ADEN)

Mme Su RUAN Génie Informatique

HCN – Hôpital Charles Nicolle HB – Hôpital de Bois-Guillaume CB – Centre Henri Becquerel

CHS – Centre Hospitalier Spécialisé du Rouvray

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Tableau 1 : Description cytologique des différents sous-types de LCM

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centrocytes et un cytoplasme peu basophile. La

basophile. La chromatine est fine et un nucléole est facilement observé. Le noyau est contourné.

Cellules de taille moyenne et assez hétérogène, rapport nucléo-cytoplasmique élevé, chromatine

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Peripheral lymphoid tissues

Pro-B cell

Pre-B-I cell

Pre-B-II cell

Immature B lymphocyte

Mature B lymphocyte Follicular germinal

centre cells Memory B cell Plasma cell Naive B cell D_H–J_H IGH _(V H–DH–JH) rearrangement

IGK _{genes rearranged}

Somatic mutations in IGH, IGK and IGL

IGL genes rearranged (mainly in lg
+ _cells)

IGH _{isotype switch}

process is characterized by

The class from the constant region IgM and IgD to IgG,

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E1
E1 E2F Deletion 9p21 Amplification 10p11 Amplification 12q13 Overexpression t(11;14)(q13;q32) Deletion 11q22-q23 Deletion CDK4 BMI1 CDK4 D1 D1 D1 p27 p27 p21 D1 INK4a RB1 P P Apoptosis Deletion 17p13 CHK2 ATM MDM2 ATR CHK1 p53 Cyclin E p27 CDK2 Cyclin E CDK2 P S G2 M G1 CDK4 D1

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