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Anne-Laure Mosca-Boidron,
Mylène Valduga,
Christel Thauvin-Robinet,
Nathalie Lagarde,
Nathalie Marle,
Céline Henry,
Jean-Michel Pinoit,
Frédéric Huet,
Mylène Béri-Deixheimer,
Clémence Ragon,
Lucie Gueneau,
Muriel Payet,
Patrick Callier, Francine Mugneret,
Philippe Jonveaux,
Laurence Faivre
American Journal of Medical Genetics Part A 04/2013; · 2.39 Impact Factor
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Anne-Laure Mosca-Boidron,
Laurence Faivre,
Serge Aho,
Nathalie Marle,
Caroline Truntzer,
Thierry Rousseau,
Clémence Ragon,
Muriel Payet,
Christelle Thauvin-Robinet,
Julien Thevenon,
Salima El Chehadeh,
Fréderic Huet,
Paul Sagot, Francine Mugneret,
Patrick Callier
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ABSTRACT: The aim of this study was to develop an improved technique for DNA extraction from 1 ml of uncultured AF from patients with a gestational age less than 16 weeks and to allow the use of array-CGH without DNA amplification. The DNA extraction protocol was tested in a series of 90 samples including 41 of uncultured AF at less than 16 weeks of gestation. Statistical analyses were performed using linear regression. To evaluate the sensitivity and the specificity of array-CGH on 1 ml of uncultured AF, five samples with an abnormal karyotype (three with aneuploidy, two with structural abnormalities) and five with a normal karyotype were studied. This protocol was reproducible and we were able to show a great improvement with higher yield of DNA obtained from all patients, including those with a gestational age less than 16 weeks (p = 0.003). All chromosomal abnormalities were detected and characterized by array-CGH and normal samples showed normal profiles. This new DNA extraction protocol associated with array-CGH analysis could be used in prenatal testing even when gestational age is less than 16 weeks, especially in cases with abnormal ultrasound findings.
PLoS ONE 01/2013; 8(4):e59956. · 4.09 Impact Factor
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Camille Leroy,
Emilie Landais,
Sylvain Briault,
Albert David,
Olivier Tassy,
Nicolas Gruchy,
Bruno Delobel,
Marie-José Grégoire,
Bruno Leheup,
Laurence Taine, [......],
Nathalie Leporrier,
Jacques Motte,
Caroline Fiquet,
Olivier Brichet,
Monique Mozelle-Nivoix,
Pascal Sabouraud,
Nathalie Golovkine,
Nathalie Bednarek,
Dominique Gaillard,
Martine Doco-Fenzy
[show abstract]
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ABSTRACT: The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable '2q37-deletion syndrome' or Albright's hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype-phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1.European Journal of Human Genetics advance online publication, 17 October 2012; doi:10.1038/ejhg.2012.230.
European journal of human genetics: EJHG 10/2012; · 3.56 Impact Factor
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Florence Nguyen-Khac,
Jerome Lambert,
Elise Chapiro,
Aurore Grelier,
Sarah Mould,
Carole Barin,
Agnes Daudignon,
Nathalie Gachard,
Stephanie Struski,
Catherine Henry, [......],
Jean Chiesa,
Marie-Joelle Mozziconacci,
Evelyne Callet-Bauchu,
Lauren Veronese,
Helene Blons,
Roger Owen,
Julie Lejeune,
Sylvie Chevret,
Helene Merle-Beral,
Veronique Leblond
[show abstract]
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ABSTRACT: Background. Waldenström macroglobulinemia is a mature B-cell disease, the genetic bases of which are poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. Design and Methods. We conducted a prospective cytogenetic study of Waldenström macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomised trial. Results. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). Trisomy of chromosomes 4 and 18 were significantly associated. Translocation involving IGH genes was rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival (PFS) and short disease-free survival (DFS). Although rare (<5%), trisomy 12 was associated with short PFS. Conclusions. The cytogenetic profile of Waldenström macroglobulinemia thus appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. The trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374.
Haematologica 10/2012; · 6.42 Impact Factor
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Violaine Havelange,
Geneviève Ameye,
Ivan Théate,
Evelyne Callet-Bauchu, Francine Mugneret,
Lucienne Michaux,
Nicole Dastugue,
Dominique Penther,
Carole Barin,
Marie-Agnès Collonge-Rame, [......],
Nathalie Nadal,
Eric Lippert,
Jean-Luc Laï,
Christine Cabrol,
Isabelle Tigaud,
Christian Herens,
Anne Hagemeijer,
Martine Raphael,
Jeanne-Marie Libouton,
Hélène A Poirel
[show abstract]
[hide abstract]
ABSTRACT: We previously showed that complex karyotypes (CK) and chromosome 13q abnormalities have an adverse prognostic impact in childhood Burkitt lymphomas/leukemias (BL) and diffuse large B-cell lymphomas (DLBCL). The aim of our study was to identify recurrent alterations associated with MYC rearrangements in aggressive B-cell lymphomas with CK. Multicolor fluorescence in situ hybridization (M-FISH) was performed in 84 patient samples (59 adults and 25 children), including 37 BL (13 lymphomas and 24 acute leukemias), 12 DLBCL, 28 B-cell lymphomas with intermediate features (DLBCL/BL), 4 B-cell precursor acute lymphoblastic leukemias (BCP-ALL), and 3 unclassifiable B-cell lymphomas. New (cytogenetically undetected) abnormalities were identified in 80% of patients. We also refined one-third of the chromosomal aberrations detected by karyotyping. M-FISH proved to be more useful in identifying chromosomal partners involved in unbalanced translocations and in revealing greater complexity of 13q rearrangements. Most of the newly identified or refined recurrent alterations involved 1q, 13q and 3q (gains/losses), 7q and 18q (gains), or 6q (losses), suggesting that these secondary aberrations may play a role in lymphomagenesis. Several patterns of genomic aberrations were identified: 1q gains in BL, trisomies 7 in DLBCL, and 18q-translocations in adult non-BL. BCP-ALL usually displayed an 18q21 rearrangement. BL karyotypes were less complex and aneuploid than those of other MYC-rearranged lymphomas. BCP-ALL and DLBCL/BL were associated with a higher rate of early death than BL and DLBCL. These findings support the categorization of DLBCL/BL as a distinct entity and suggest that BL with CK are indeed different from other aggressive MYC-rearranged lymphomas, which usually show greater genetic complexity. © 2012 Wiley Periodicals, Inc.
Genes Chromosomes and Cancer 09/2012; · 3.31 Impact Factor
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Cecile Borel,
Nicole Dastugue,
Valérie Cances-Lauwers,
Marie-Joelle Mozziconacci,
Thomas Prebet,
Norbert Vey,
Aranud Pigneux,
Eric Lippert,
Sorin Visanica,
Faezeh Legrand,
Jean Philippe Rault,
Sylvie Taviaux,
Christian Bastard, Francine Mugneret,
Marie Agnes Collonges Rames,
Nathalie Gachard,
Pascaline Talmant,
Eric Delabesse,
Christian Récher
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ABSTRACT: The PICALM-MLLT10 fusion gene, generated by the t(10;11)(p12-13;q14-21) translocation, is a rare but recurrent event in acute leukemias. In this study, we assessed the characteristics and outcome of 18 PICALM-MLLT10 AML patients. As compared with non PICALM-MLLT10 patients (n=72), PICALM-MLLT10 AML were characterized by more frequent extramedullary diseases, CD7 expression and higher platelet counts. Three out of four therapy-related PICALM-MLLT10 AMLs had been previously treated for diffuse large B-cell lymphoma. The complete response rate was 71% after intensive chemotherapy. PICALM-MLLT10 patients had a shorter median overall survival than patients with favorable cytogenetics (12months vs. not reached, p=0.07) but not significantly different from those of intermediate (26months, p=0.32) or unfavorable cytogenetic groups (8months, p=0.13). Long term responses were achieved in a subset of patients after allogeneic stem-cell transplantation but also after high-dose cytarabine.
Leukemia research 08/2012; 36(11):1365-9. · 2.36 Impact Factor
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Julien Thevenon,
Patrick Callier,
Joris Andrieux,
Bruno Delobel,
Albert David,
Sylvie Sukno,
Delphine Minot,
Laure Mosca Anne,
Nathalie Marle,
Damien Sanlaville, [......],
Fabienne Levy,
Lorraine Gaunt,
Sandra Farrell,
Cédric Le Caignec,
Annick Toutain,
Virginie Carmignac, Francine Mugneret,
Jill Clayton-Smith,
Christel Thauvin-Robinet,
Laurence Faivre
[show abstract]
[hide abstract]
ABSTRACT: Speech sound disorders are heterogeneous conditions, and sporadic and familial cases have been described. However, monogenic inheritance explains only a small proportion of such disorders, in particular in cases with childhood apraxia of speech (CAS). Deletions of <5 Mb involving the 12p13.33 locus is one of the least commonly deleted subtelomeric regions. Only four patients have been reported with such a deletion diagnosed with fluorescence in situ hybridisation telomere analysis or array CGH. To further delineate this rare microdeletional syndrome, a French collaboration together with a search in the Decipher database allowed us to gather nine new patients with a 12p13.33 subtelomeric or interstitial rearrangement identified by array CGH. Speech delay was found in all patients, which could be defined as CAS when patients had been evaluated by a speech therapist (5/9 patients). Intellectual deficiency was found in 5/9 patients only, and often associated with psychiatric manifestations of various severity. Two such deletions were inherited from an apparently healthy parent, but reevaluation revealed abnormal speech production at least in childhood, suggesting variable expressivity. The ELKS/ERC1 gene, which encodes for a synaptic factor, is found in the smallest region of overlap. These results reinforce the hypothesis that deletions of the 12p13.33 locus may be responsible for variable phenotypes including CAS associated with neurobehavioural troubles and that the presence of CAS justifies a genetic work-up.European Journal of Human Genetics advance online publication, 20 June 2012; doi:10.1038/ejhg.2012.116.
European journal of human genetics: EJHG 06/2012; · 3.56 Impact Factor
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ABSTRACT: We report a new case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with extensive immunophenoptyping, genotyping (karyotype, array-comparative genomic hybridization, and fluorescent in situ hybridization), and long-term tumor cells culture. BPDCN is a very rare and aggressive disease clinically characterized by a skin revealing localization more or less rapidly disseminating to the bone marrow and other organs with or without and leukemia. The disease was initially phenotypically characterized by the expression of both CD4 and CD56 antigens, whereas lymphoid and myeloid lineage antigens were negative. A phenotypic link with alpha-interferon (IFN-I)-producing plasmacytoid dendritic cells was demonstrated. The data collected in this case report provide additional biological and genotypical data on tumor cells of BPDCN. This study confirms the capability of tumor cells to secrete IFN-I, demonstrated by biological IFN-I activity of cultured cells and immunohistochemical expression of Mx-1 protein. Although a common genetic profile involving chromosomes 5, 6, 9, 12, 13, and 15 has been identified, no specific genetic marker has been demonstrated that is specific to BPDCN. The demonstration of ETV6 gene deletion in this case deserves further investigations as a putative BPDCN marker.
The American Journal of dermatopathology 04/2012; 34(6):626-31. · 1.30 Impact Factor
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ABSTRACT: GRIA3 encodes glutamate receptor ionotropic AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subunit 3 and has been previously involved in X-linked intellectual disability (ID). We report on a male proband with ID and epilepsy associated with a duplication mapping within a gene desert, 874-kb upstream of the GRIA3 gene. This 970-kb duplication is maternally inherited. The proband's mother has a skewed X chromosome-inactivation pattern in agreement with her normal cognitive function. Quantitative polymerase chain reaction analysis indicates absence of GRIA3 mRNA in the proband lymphocytes relative to a wild-type control. Centromeric to the duplicated region, comparative genomic analysis showed a 2268-bp evolutionarily conserved region that could be a critical transcription factor binding-site for GRIA3 expression. The repositioning of distant-acting sequences, rather a missense/nonsense mutation, is considered to be causative for GRIA3-linked ID. This study illustrates the importance of high-resolution array-Comparative Genomic Hybridization analysis in exploring the potential role of disease-causing mutation in functional noncoding sequences.
Human Mutation 11/2011; 33(2):355-8. · 5.69 Impact Factor
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Francois P Duhoux,
Geneviève Ameye,
Carmen P Montano-Almendras,
Khadija Bahloula,
Marie J Mozziconacci,
Sophy Laibe,
Iwona Wlodarska,
Lucienne Michaux,
Pascaline Talmant,
Steven Richebourg, [......],
Katrina Rack, Francine Mugneret,
Isabelle Tigaud,
Marina Lafage,
Sylvie Taviaux,
Catherine Roche-Lestienne,
Dominique Latinne,
Jeanne M Libouton,
Jean-Baptiste Demoulin,
Hélène A Poirel
[show abstract]
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ABSTRACT: The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.
British Journal of Haematology 11/2011; 156(1):76-88. · 4.94 Impact Factor
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Aurore Perrot,
Isabelle Luquet,
Arnaud Pigneux, Francine Mugneret,
Jacques Delaunay,
Jean-Luc Harousseau,
Carole Barin,
Jean-Yves Cahn,
Philippe Guardiola,
Chantal Himberlin,
Christian Recher,
Norbert Vey,
Bruno Lioure,
Mario Ojeda-Uribe,
Nathalie Fegueux,
Christian Berthou,
Edouard Randriamalala,
Marie C Béné,
Norbert Ifrah,
Francis Witz
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ABSTRACT: The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK(+) patients had a complete response rate significantly lower than MK(-) patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK(+) patients, survival was dramatically decreased for MK(+) patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.
Blood 05/2011; 118(3):679-85. · 9.90 Impact Factor
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Salima El Chehadeh-Djebbar,
Patrick Callier,
Alice Masurel-Paulet,
Candace Bensignor,
Nathalie Méjean,
Muriel Payet,
Clémence Ragon,
Christine Durand,
Nathalie Marle,
Anne-Laure Mosca-Boidron,
Frédéric Huet, Francine Mugneret,
Laurence Faivre,
Christel Thauvin-Robinet
[show abstract]
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ABSTRACT: We report the case of a 26-month-old boy with mental retardation, facial dysmorphism, childhood feeding difficulties, short stature, bilateral cryptorchidism, micropenis, and heart defect. Endocrinal evaluation revealed complete growth hormone deficiency (GHD) and gonadotropic deficiency, and pituitary magnetic resonance imaging showed partial pituitary stalk interruption syndrome (PSIS). A de novo 493 kb microdeletion on chromosome 17q21.31 was identified using array comparative genomic hybridization (array-CGH) analysis. This is the first report of PSIS in the phenotypical spectrum of 17q21.31 microdeletion syndrome, although other midline abnormalities have previously been described. Our report suggests that GHD should be investigated in patients with 17q21.31 microdeletion syndrome and short stature, defined by a body height below - 2 standard deviation scores (SDS) for age and sex. This finding also opens new avenues of research on the etiopathogenesis of PSIS, for which the genetic mechanisms remain unknown.
European journal of medical genetics 03/2011; 54(3):369-73. · 1.57 Impact Factor
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Salima El Chehadeh-Djebbar,
Laurence Faivre,
Anne Moncla,
Bernard Aral,
Chantal Missirian,
Cornel Popovici,
Patrick Rump,
Anthonie Van Essen,
Anne-Marie Frances,
Nadège Gigot, [......],
Muriel Payet,
Clémence Ragon,
Nathalie Marle,
Anne-Laure Mosca-Boidron,
Frédéric Huet,
Irina Balikova,
Jean-Raymond Teyssier, Francine Mugneret,
Christel Thauvin-Robinet,
Patrick Callier
Journal of Medical Genetics 02/2011; 48(11):e1. · 6.36 Impact Factor
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Francois P Duhoux,
Geneviève Ameye,
Virginie Lambot,
Christian Herens,
Frédéric Lambert,
Sophie Raynaud,
Iwona Wlodarska,
Lucienne Michaux,
Catherine Roche-Lestienne,
Elise Labis, [......], Francine Mugneret,
Isabelle Tigaud,
Marie-Joëlle Mozziconacci,
Sophy Laibe,
Nathalie Nadal,
Christine Terré,
Jeanne-Marie Libouton,
Anabelle Decottignies,
Miikka Vikkula,
Hélène A Poirel
PLoS ONE 01/2011; 6(12). · 4.09 Impact Factor
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Julien Thevenon,
Patrick Callier,
Christel Thauvin-Robinet,
Nathalie Mejean,
Sylvie Falcon-Eicher,
Marc Maynadie,
Emmanuel de Maistre,
Samuel Bidot,
Frédéric Huet,
Mylène Beri-Dexheimer,
Philippe Jonveaux, Francine Mugneret,
Laurence Faivre
American Journal of Medical Genetics Part A 01/2011; 155A(1):126-9. · 2.39 Impact Factor
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Francois P Duhoux,
Geneviève Ameye,
Virginie Lambot,
Christian Herens,
Frédéric Lambert,
Sophie Raynaud,
Iwona Wlodarska,
Lucienne Michaux,
Catherine Roche-Lestienne,
Elise Labis, [......], Francine Mugneret,
Isabelle Tigaud,
Marie-Joëlle Mozziconacci,
Sophy Laibe,
Nathalie Nadal,
Christine Terré,
Jeanne-Marie Libouton,
Anabelle Decottignies,
Miikka Vikkula,
Hélène A Poirel
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ABSTRACT: Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.
PLoS ONE 01/2011; 6(10):e26311. · 4.09 Impact Factor
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Florence Nguyen-Khac,
Elise Chapiro,
Claude Lesty,
Aurore Grelier,
Isabelle Luquet,
Isabelle Radford-Weiss,
Christine Lefebvre,
Sandra Fert-Ferrer,
Evelyne Callet-Bauchu,
Eric Lippert, [......],
Stéphanie Struski,
Pascaline Talmant,
Laurence Baranger,
Nathalie Gachard,
Carine Gervais,
Benoit Quilichini,
Catherine Settegrana,
Karim Maloum,
Frederic Davi,
Hélène Merle-Béral
[show abstract]
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ABSTRACT: Chromosomal translocations are usually analyzed as a single entity, and are associated with a poor outcome in chronic lymphocytic leukemia. Translocations involving immunoglobulin genes are recurrent, but uncommon (<5%), and their individual prognosis is not clear. The two most frequent partners are BCL2 (18q21) and BCL3 (19q13).
Herein, 75 cases are reported of chronic lymphocytic leukemia and t(14;18) (BCL2-CLLs). Our series benefits from morphological, immunological and cytogenetical reviews. The IGHV status analyses were performed by referring laboratories. Comparison was made with our previously published series of chronic lymphocytic leukemia patients with t(14;19) (BCL3-CLLs, n=29).
Compared with BCL3-CLLs, lymphocytosis was lower in BCL2-CLLs (p<0.008), and splenomegaly was less frequent (p<0.0001). There were more "typical" morphologies (p<0.005) and Matutes scores >4 (p<0.001) in the BCL2-CLLs group, and less CD38 expression (p<0.04). More variant BCL2-translocations were observed (t(18;22), n=11; 2t(2;18), n=2; p<0.02), and BCL2-translocation was frequently single (p<0.002). Complex karyotypes (p<0.02), trisomy 12 (p<0.03), 6q deletion (p<0.002) and TP53 deletion (p<0.02) were less frequent in BCL2-CLLs, whereas 13q deletion was more frequent (p<0.005). The IGHV gene was frequently mutated in BCL2-CLLs (p<0.0001). Treatment-free survival was longer in BCL2-CLLs (p<0.0001).
BCL2-CLL.S express CD5 and lack expression of CD38, and have a Matutes score ≥4, frequent trisomy 12, no ATM and 6q deletions, and a mutated IGHV status. Compared to BCL3-CLLs, BCL2-CLLs are much less aggressive; indicating that identifying individual translocations and cytogenetic partners would allow improved patient stratification.
American journal of blood research. 01/2011; 1(1):13-21.
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Florence Nguyen-Khac,
Claude Lesty,
Virginie Eclache,
Lucile Couronné,
Olivier Kosmider,
Joris Andrieux,
Marie-Agnes Collonge-Rame,
Dominique Penther,
Marina Lafage,
Chrystele Bilhou-Nabera,
Elise Chapiro,
Marie-Joelle Mozziconacci, Francine Mugneret,
Nathalie Gachard,
Nathalie Nadal,
Eric Lippert,
Stephanie Struski,
Nicole Dastugue,
Christine Cabrol,
Olivier A Bernard
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ABSTRACT: Evolution to myelofibrosis (MF), acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) may occur over time in myeloproliferative neoplasms (MPN) patients most likely due to the acquisition of additional mutations. The Groupe Francophone de cytogenetique hematologique (GFCH) has collected and reviewed 82 patients with transformation of MPN (66 AML/MDS and 16 MF). JAK2V617F and TET2 mutations were searched for in 40 and 32 patients, respectively. Significantly more -7/del(7q) (P = 0.004) and -5/del(5q) (P = 0.03) were found in AML/MDS with a higher incidence of dup1q (P = 0.01) in MF. Some specific chromosomal abnormalities occurred together, for example -5/del(5q) and -17/del(17p) (P = 0.0007). In multivariate analysis, two factors were independently associated with an inferior overall survival (OS); AML/MDS transformation (P < 0.0001) and -5/del(5q) abnormality (P = 0.02). Although both giving rise to loss of 7q, der(1;7) differed from other 7q deletions in terms of distribution (lower frequency of AML/MDS, P = 0.02), association with chromosomal abnormalities (absence of -5/del(5q), P = 0.003; increased del(20q), P = 0.05), and longer OS (P = 0.0007). We detected 24/40 (60%) JAK2V617F and 8/25 (32%) TET2 mutations in samples following transformation, ranging from wild-type to mutated forms of both genes. The mutated and wild-type forms of the genes were not found to be associated with a specific chromosomal abnormality. There was no evidence that JAK2 or TET2 mutations were associated with the type of MPN transformation, whereas the type of cytogenetic abnormalities were strongly linked, perhaps indicating that they play a specific role in the transformation process.
Genes Chromosomes and Cancer 10/2010; 49(10):919-27. · 3.31 Impact Factor
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Marc Maynadié,
François Girodon,
Ines Manivet-Janoray,
Morgane Mounier, Francine Mugneret,
François Bailly,
Bernardine Favre,
Denis Caillot,
Tony Petrella,
Michel Flesch,
Paule-Marie Carli
[show abstract]
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ABSTRACT: Epidemiological data on myeloid malignancies are very rare in the literature due to a lack of registration by cancer registries until 2000. The Registry of Hematologic Malignancies of the Côte d'Or Department in France has, however, steadfastly registered data on cases occurring in the Department since 1980, resulting, to date, in a database of over 5,000 cases classified according to the ICD-O-3 classification, following the most recent World Health Organization classification criteria.
Twenty-five years of data on myeloid malignancies, including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes were analyzed. World population standardized incidence rates were calculated as were as observed and relative survival.
Incidence rates per 100,000 inhabitants/year were 2.5 for acute myeloid leukemia, 1.3 for myelodysplastic syndromes, 3.2 for myeloproliferative neoplasms and 0.6 for myelodysplastic/myeloproliferative syndromes. It was found that the incidence rate of myelodysplastic syndromes increased significantly over the period. The median overall survival is 8.9 months for patients with acute myeloid leukemia, 33.8 months for patients with myelodysplastic syndromes, 91.7 months for those with myeloproliferative neoplasms and 26.6 months for patients with myelodysplastic/myeloproliferative syndromes. Observed and relative 20-year survival rates are, respectively, 12% and 13% in acute myeloid leukemia, 2% and 6% in myelodysplastic syndromes and 20% and 34% in myeloproliferative neoplasms.
These population-based data on myeloid malignancies are the first data collected over such a long period and provide interesting information for clinicians and public health authorities, particularly given the paucity of other long-term, population-based data from cancer registries.
Haematologica 10/2010; 96(1):55-61. · 6.42 Impact Factor
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Etienne Coyaud,
Stephanie Struski,
Nais Prade,
Julien Familiades,
Ruth Eichner,
Cathy Quelen,
Marina Bousquet, Francine Mugneret,
Pascaline Talmant,
Marie-Pierre Pages, [......],
Carole Barin,
Marie-Joëlle Mozziconacci,
Marina Lafage-Pochitaloff,
Hélène Antoine-Poirel,
Christiane Charrin,
Christine Perot,
Christine Terre,
Pierre Brousset,
Nicole Dastugue,
Cyril Broccardo
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ABSTRACT: PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases. To isolate fusion partners, we used classic and innovative techniques (rolling circle amplification-rapid amplification of cDNA ends) and single nucleotide polymorphism-comparative genomic hybridization arrays. Recurrent and novel fusion partners were identified, including NCoR1, DACH2, GOLGA6, and TAOK1 genes showing the high variability of the partners. We noted that half the fusion genes can give rise to truncated PAX5 proteins. Furthermore, malignant cells carrying PAX5 fusion genes displayed a simple karyotype. These data strongly suggest that PAX5 fusion genes are early players in leukemogenesis. In addition, PAX5 deletion was observed in 60% of B-ALL with 9p alterations. Contrary to cases with PAX5 fusions, deletions were associated with complex karyotypes and common recurrent translocations. This supports the hypothesis of the secondary nature of the deletion. Our data shed more light on the high variability of PAX5 alterations in B-ALL. Therefore, it is probable that gene fusions occur early, whereas deletions should be regarded as a late/secondary event.
Blood 02/2010; 115(15):3089-97. · 9.90 Impact Factor
