CCND2 rearrangements are the most frequent genetic events in cyclin D1− mantle cell lymphoma

Salaverría, Itziar; Royo, Cristina; Carvajal-Cuenca, Alejandra; Clot, Guillem; Navarro, Alba; Valera, Alejandra; Song, Joo Y.; Woroniecka, Renata; Rymkiewicz, Grzegorz; Klapper, Wolfram; Hartmann, Elena; Sujobert, Pierre; Włodarska, Iwona; Ferry, Judith A.; Gaulard, Philippe; Ott, German; Rosenwald, Andreas; López‐Guillermo, Armando; Quintanilla-Martı́nez, Leticia; Harris, Nancy L.; Jaffe, Elaine S.; Siebert, Reiner; Campo, Elı́as; Beà, Sı́lvia

doi:10.1182/blood-2012-08-452284

Cited by 178 publications

(120 citation statements)

References 31 publications

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“…Array comparative genomic hybridization was outsourced to Quantitative Genomic Medicine Laboratories (qGenomics, Spain). As previously described by Salaverria et al 17 'Protocol Version 3.1′ was followed with slight modifications. Briefly, after digestion, the DNA was fragmented (99°C for 40 min) and labeled.…”

Section: Dna Extraction and Array Comparative Genomic Hybridizationmentioning

confidence: 99%

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

et al. 2015

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Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65%), small-to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2 + (60%), CD3e + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR)β + (10%), TCRγ + (35%), TCRγδ + (50%), and double negative for TCR (six cases, 30%). All cases were EBER − . The genomic profile showed recurrent copy number gains of 1q32. 3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8 + CD56 + phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.

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Section: Dna Extraction and Array Comparative Genomic Hybridizationmentioning

confidence: 99%

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

et al. 2015

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“…1 SOX11 is a transcription factor overexpressed in the vast majority of mantle cell lymphoma, including cyclin D1-negative cases, but it is absent in most other mature B-cell lymphomas, with the exception of some Burkitt lymphomas. [2][3][4][5][6] The potential implication of SOX11 in the aggressive behavior of mantle cell lymphoma was initially suggested when it was recognized as one of the genes highly expressed in tumors requiring treatment at diagnosis compared with cases with a very indolent clinical course. 7 The relationship between the absence of SOX11 expression and an indolent clinical behavior of these tumors has been confirmed in subsequent studies [8][9][10] but not in others.…”

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Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype

et al. 2015

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Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B-cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (Po0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P = 0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P = 0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor.

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“…11 In addition, these cases often exhibit high expression of cyclin D2 or cyclin D3. 12,13 Prognostic Markers in MCL Several factors are useful to predict the outcome. Some are related to the patient's characteristics, and some reflect the tumor burden and/or the cell proliferation.…”

Section: Diagnosis and Pitfallsmentioning

confidence: 99%

“…6,19 Furthermore, these patients have a characteristic clinical and biological presentation with isolated splenomegaly and circulating leukemic cells expressing SOX11. 6,[11][12][13][14][15][16][17][18][19][20][21][22][23] Treatment for young patients (65 years). First-line strategy.…”

Section: Treatment Options In MCLmentioning

confidence: 99%

Mantle Cell Lymphoma: Individualizing Therapy

Bouabdallah¹,

Milpied²

2015

Lymphoma and Chronic Lymphocytic Leukemias

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Despite substantial improvements in the management and treatment of mantle cell lymphoma (MCL), the disease is still considered incurable. While high-dose cytarabine followed by autologous stem cell transplantation (ASCT) is considered as the gold standard in younger patients, the Rituximab, Cyclophosphomide, Doxorubicin, Oncovin, Prednisone (R-CHOP) regimen followed by rituximab maintenance is the recommended treatment for the elderly. Our better understanding of the pathogenesis of the disease through the identification of different altered signaling pathways has contributed to the development of new-targeted therapies offering a new era in the management of MCL. Early results achieved with these therapies are promising. However, new questions are arising regarding how and when to use these agents. This paper reviews these different approaches in patients with MCL.

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CCND2 rearrangements are the most frequent genetic events in cyclin D1− mantle cell lymphoma

Abstract: Key Points• This report describes a multidisciplinary study characterizing the largest series of cyclin D1 Ϫ MCL patients.• CCND2 translocations are the most frequent genetic event (55%) in cyclin D1 Ϫ MCL.

Cited by 178 publications

References 31 publications

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan

Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype

Mantle Cell Lymphoma: Individualizing Therapy

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