Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals   Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA


do you wish to send a case report ?


CASE REPORTS in HAEMATOLOGY
(Paper co-edited with the European LeukemiaNet)
The t(2;12)(p12;p13), leading to the juxtaposition of the cyclin D2 CCND2 gene with the immunoglobulin kappa locus (IGK), defines a small subset of mantle cell lymphomas lacking cyclin D1 expression.
 
Written2015-02Nicolas Duployez, Laurent Pascal, Judith Bruge, Marie Fatoux, Catherine Roche-Lestienne
Institut de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU, Avenue E Avinée, 59037 Lille, (ND, CRL); Service d'Onco-Hématologie, GHICL Hopital St Vincent de Paul, Bd de Belfort, 59020 Lille, (LP) France; Laboratoire de Biologie, GHICL, Rue du Grand But B.P. 249, 59462 Lomme Cedex, (JB, MF) France. nicolas.duployez@chru-lille.fr; pascal.laurent@ghicl.net; bruge.judith@ghicl.net; marie.fatoux@gmail.com; catherine.roche@chru-lille.fr
Clinics
Age and sex : 89 year(s) old female patient.
Previous History : no preleukemia
no previous malignant disease
no inborn condition of note
Organomegaly : no hepatomegaly ; splenomegaly ((moderate)); enlarged lymph nodes ; no central nervous system involvement
Blood
WBC : 144 x 109/L ((lymphoma cells : 93%) Morphology showed small to medium sized lymphoid cells with pale cytoplasm and slightly to markedly irregular nuclear contour sometimes mimicking centrocytes. Nucleoli were inconspicuous or absent.); Hb : 12.8 g/dL ; platelets : 196 x 109/L; blasts : NA % .
Bone marrow : Bone marrow involvement (stage IV Ann Arbor).
Note : Rapid progression of the disease because 6 months ago laboratory analyses were normal (notably blood count).
Cyto pathology classification
Phenotype : NA
Immunophenotype : lymphoma cells CD19+ CD5+ CD20+ (strong), CD22+ (strong), CD23+, FMC7+, monotypic kappa light-chain expression (moderate); Matutes score = 2/5.
Rearranged Ig Tcr : Not performed.
Pathology : Mantle cell lymphoma
Electron microscopy : Not performed.
Precise diagnosis : Mature B-cell neoplasm, cyclin D1-negative mantle cell lymphoma.
Survival
Date of diagnosis: 10-2014
Treatment : 10/2014: Patient first received chloraminophene and rituximab (2 courses). 12/2014: Patient was then treated with ibrutinib (140 mg x 4/day).
Complete remission : None
Treatment related death : -
Relapse : -
Status : Dead 01-2015
Survival : 4 month(s)
Karyotype
Sample : Bone marrow ; culture time : 96 h, DSP30/IL2 ; banding : GTG
Results : 45,XX,t(2;12)(p12;p13),add(9)(p13),add(11)(q23),-22[7]/46,XX[7]
Other molecular cytogenetics technics : FISH
Other molecular cytogenetics results : 45,XX,t(2;12)(p12;p13). ish der(2)t(2;12)(WCP12p+), der(12)t(2;12)(WCP12p+)[2].
Other molecular studies
technics : CCND1 (BCL1) expression evaluated by RT-PCR.
results : No CCND1 overexpression.
Partial GTG-banding karyotype of the t(2;12)(p12;p13).
FISH analysis of the t(2;12)(p12;p13)translocation, using painting probe of the short arm of chromosome 12 (WCP12p probe)in green. Arrows indicate the der(2) and der(12) chromosomes.
FISH analysis of the t(2;12) translocation, using BAC probe CCND2 RP11-264F23 in red and BAC probe RP11-530J6 located at 2q33 in green. Figure 3A is a normal metaphase and Figure 3B revealed the der(2) chromosome harboring CCND2 red signal.
Leukemic phase of mantle cell lymphoma. Peripheral blood. Small to medium sized lymphoid cells with pale cytoplasm and slightly too markedly irregular nuclear contour, sometimes mimicking centrocytes. From a patient with 46,XX,t(2;12)(p12;p13).
Comments
According to the WHO classification of hematopoietic tumours, mantle cell lymphoma (MCL) is defined as a B-cell neoplasm composed of monomorphic small to medium-sized lymphoid cells with a CCND1 (cyclin D1) translocation. In recent years, it has been observed a small subset of lymphomas resembling conventional MCL both morphologically and phenotypically, with a similar gene expression profile but lacking the CCND1 translocation (Fu et al, Blood, 2005). In 2013, Salaverria et al. investigated 40 well-defined CCDN1-negative MCL and identified 22 cases (55%) with CCND2 (cyclin D2) translocations (Salaverria et al, Blood, 2013). Interestingly, it was noted that CCND2 predominantly translocates to IG light chain genes (15/22, 68%) in contrast with CCND1 translocations. Finally, in CCND1-negative MCL, the identification of CCND2 gene rearrangement provides a very robust marker for diagnosis.
Internal links
Atlas Cardt(2;12)(p12;p13) IGK/CCND2
Bibliography
Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling.
Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Müller-Hermelink HK, Campo E, Gascoyne RD, Staudt LM, Chan WC; Lymphoma/Leukemia Molecular Profiling Project
Blood. 2005 Dec 15;106(13):4315-21. Epub 2005 Aug 25.
PMID 16123218
 
CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma.
Salaverria I, Royo C, Carvajal-Cuenca A, Clot G, Navarro A, Valera A, Song JY, Woroniecka R, Rymkiewicz G, Klapper W, Hartmann EM, Sujobert P, Wlodarska I, Ferry JA, Gaulard P, Ott G, Rosenwald A, Lopez-Guillermo A, Quintanilla-Martinez L, Harris NL, Jaffe ES, Siebert R, Campo E, Beà S.
Blood. 2013 Feb 21;121(8):1394-402. doi: 10.1182/blood-2012-08-452284. Epub 2012 Dec 18
PMID 23255553
 

Citation

This paper should be referenced as such :
Duployez N, Pascal L, Bruge J, Fatoux M, Roche-Lestienne C
The t(2;12)(p12;p13), leading to the juxtaposition of the cyclin D2 CCND2 gene with the immunoglobulin kappa locus (IGK), defines a small subset of mantle cell lymphomas lacking cyclin D1 expression.
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Reports/t0212p12p13DuployezID100081.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jan 18 15:23:20 CET 2017


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals   Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.