T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10

Liu, Hongxiang; Ye, Hongtao; Doğan, Ahmet; Ranaldi, Renzo; Hamoudi, Rifat; Bearzi, Italo; Isaacson, Peter G.; Du, Ming

doi:10.1182/blood.v98.4.1182

Cited by 229 publications

(225 citation statements)

References 47 publications

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“…7,[27][28][29][30] In MALT lymphoma, deregulation of the expression of MALT1 gene due to chromosomal translocations t(11;18)(q21; q21) and t(14;18)(q32;q21) seems to be one of the main pathogenic mechanisms leading to reduced apoptotic activity. 12,15,22,[31][32][33] In contrast to what has been described in gastric MALT lymphomas, our results did not indicate the presence of t (11;18). This translocation has been extensively examined in gastric MALT lymphomas and is associated with cases of a more advanced stage or those lacking responses to Helicobacter pylori eradication.…”

Section: Discussioncontrasting

confidence: 99%

“…Under physiological conditions bcl10 plays a dual pro-and antiapoptotic role. 12,15,[31][32][33]35 The nuclear expression of bcl10 has been proposed as a surrogate of NF-kB activation after (11;18)(q21;q21), t(1;14)(p22;q32), while strong cytoplasmic expression has been linked with t(14;18)(q32;q21). 7,12,22,35,36 Strikingly, our data show a clear association between nuclear bcl10, increased expression of p-IkBa, and shorter time to failure.…”

Section: Discussionmentioning

confidence: 99%

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Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Franco

Camacho

Caleo³

et al. 2006

Modern Pathology

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Ocular adnexa B-cell lymphomas are a relatively rare group of extranodal lymphomas, marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) being the most frequent type at this location. As with other nongastrointestinal MALT lymphomas, ocular adnexa MALT lymphomas have distinct characteristics from those of the gastric MALT model, implying specific pathogenic events, which could be of interest in the prediction of clinical behavior and the choice between therapeutic options. In a series of 39 cases of ocular adnexa MALT lymphomas, studied using a tissue microarray, we observed that the most frequent alteration was related to apoptosis regulation. Thus, caspase 3 activity was completely abolished, and phosphorylated IjBa, a marker of NF-jB activation, showed increased expression, while cases with an increased number of large cells displayed increased expression of survivin and other cell-cycle-related proteins, such as cyclin A, cyclin E and Ki67, and p16 expression was reduced. There were no occurrences of t(11;18)(q21,q21), while 5/37 cases exhibited t(14;18)(q32;q21). Aberrant nuclear expression of bcl10 was observed in 11 cases, independently of the presence of translocations, and was significantly associated with phosphorylated IjBa expression and a reduced TdT-mediated biotin-dUTP nicked-end labeling apoptotic index. Moreover, patients with tumoral bcl10 nuclear expression showed shorter failure-free survival.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Franco

Camacho

Caleo³

et al. 2006

Modern Pathology

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“…Our data showed that the VH usage pattern, which does not change in the course of tumor progression, was significantly different between tumors that were dependent on inflammation and those that were not. This finding suggests that such progression may not commonly occur, and further supports the hypothesis that API2-MALT1 fusion-positive tumors (Group C), which are often negative for H. pylori infection 8,11 and resistant to eradication, 8,10 may arise independently of chronic inflammation.…”

Section: Discussionsupporting

confidence: 75%

“…Some of these features have been reported by other investigators as well. [9][10][11] These findings suggest that Group A tumors are considerably different from those of Groups B or C in their clinicopathological features.…”

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confidence: 91%

Immunoglobulin VH gene analysis in gastric MALT lymphomas

et al. 2007

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The majority of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are successfully treated with Helicobacter pylori eradication alone. However, certain subsets of these tumors are resistant to the eradication treatment. As API2-MALT1 fusion is a feature of one of these subsets, we divided gastric MALT lymphomas into three groups: eradication-responsive and API2-MALT1 fusion-negative (Group A), eradication-resistant and fusion-negative (Group B), and eradication-resistant and fusion-positive (Group C). To characterize further gastric MALT lymphomas, we analyzed VH genes, which do not change in the course of tumor progression, by extensive subcloning of the monoclonal PCR products of 45 cases. VH3-23 and VH3-30 were preferentially used in Group A tumors (14/23 cases, 61%) as compared with Group B (1/10 cases, 10%, P ¼ 0.0094) and Group C (2/ 12 cases, 17%, P ¼ 0.017). Tumors of Groups B and C used variegated VH fragments, and no dominant VH fragments were noted. Somatic mutation was detected in most of the cases. Ongoing mutation was detected in 3/45 cases (7%), when assessed according to strict criteria for a confirmed mutation. These findings suggest that inflammation-dependent tumors (Group A) may be derived from a highly restricted, probably H. pyloriassociated, B cell subset and may not often progress to those that are inflammation-independent (Groups B and C). Although considered to be common in this tumor, ongoing mutation may be infrequent when assessed by strict criteria. Keywords: gastric MALT lymphoma; helicobacter pylori; eradication; immunoglobulin heavy chain variable genes; API2-MALT1 fusion gene Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct low-grade lymphoma, which is typically localized long term at the site of origin. 1 A preexisting chronic inflammation, such as Helicobacter pylori gastritis, Hashimoto's thyroiditis, or Sjogren's syndrome is considered to influence significantly its development. 1 The etiological link between gastric MALT lymphoma and H. pylori gastritis has arisen from the fact that the majority of gastric MALT lymphomas (approximately 70% of cases) show complete regression on eradication of H. pylori alone. 2 API2-MALT1 fusion, cloned from t(11;18)(q21;q21), is a gene alteration specific to MALT lymphomas. 3,4 API2 is a member of the IAP (inhibitor of apoptosis) gene family, and is essential for the suppression of apoptosis. 5 MALT1, a novel

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“…12 Four mutually exclusive and apparently sitespecific, chromosomal translocations have been implicated in the development and progression of extranodal marginal zone lymphoma of mucosaassociated lymphoid tissue. These extranodal marginal zone lymphoma-associated translocations, t(11;18)(q21;q21), 11,[13][14][15][16][17][18][19][20][21][22] t(1;14)(p22;q32), 13,14,23 t(14;18) (q32;q21) 14,15,24,25 and t(3;14)(p14.1;q32) 26 show substantial differences in prevalence at specific extranodal localizations. In addition, several studies have reported the presence of various cytogenetic numerical aberrations, including trisomy 3, 7, 12 and 18, in extranodal marginal zone lymphoma at different extranodal sites.…”

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confidence: 99%

T(14;18)(q32;q21) involving MALT1 and IGH genes occurs in extranodal diffuse large B-cell lymphomas of the breast and testis

et al. 2013

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Primary B-cell lymphoma of the testis, breast and thyroid are rare and data concerning cytogenetic aberrations at these extranodal sites are scarce. We examined the presence of extranodal marginal zone lymphomaassociated translocations, t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(p14.1;q32) and numerical aberrations of chromosomes 1, 3, 12 and 18 by fluorescence in situ hybridization in 6 extranodal marginal zone lymphomas and 24 diffuse large B-cell lymphomas with (n ¼ 9) or without (n ¼ 15) marginal zone lymphoma components, with primary localizations in the breast (n ¼ 15), testis (n ¼ 9) and thyroid (n ¼ 6). We found t(14;18)(q32;q21), with breakpoints in IGH and MALT1, in one testicular diffuse large B-cell lymphoma and in two diffuse large B-cell lymphomas of the breast. No other translocations, amplifications or deletions involving IGH, BCL-10, BCL-2, MALT1 and IAP2 were detected. Numerical aberrations occurred in 67% of the lymphomas, 67% of extranodal marginal zone lymphomas, 56% of diffuse large B-cell lymphomas with marginal zone lymphoma components and in 73% of 'de novo' diffuse large B-cell lymphomas. These included 78% of testis, 67% of thyroid and 60% of breast lymphomas, and included mainly trisomy 18 (n ¼ 16), trisomy 3 (n ¼ 8) and trisomy 1 (n ¼ 3). One testicular diffuse large B-cell lymphoma harbored both t(14;18)(q32;q21) and trisomy 3. Our results indicate that at least a few cases of diffuse large B-cell lymphoma of the testis and the breast belong to the spectrum of extranodal marginal zone lymphoma. Modern Pathology (2013) 26, 421-427; doi:10.1038/modpathol.2012; published online 28 September 2012Keywords: B-cell lymphoma; FISH; IGH; MALT1; numerical chromosomal aberrations; translocations Primary B-cell lymphoma of the testis, breast and thyroid are rare, each accounting for between 0.5 and 2.5% of all non-Hodgkin's lymphomas (NHLs). [1][2][3][4][5][6] Diffuse large B-cell lymphoma is the most common histological entity at these extranodal sites. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, commonly found in extranodal sites devoid of native lymphoid tissue, like the stomach, lung, salivary gland, thyroid and ocular adnexa, occur infrequently in the breast and testis. Although extranodal marginal zone lymphoma and diffuse large B-cell lymphoma are considered distinct clinicopathological entities in the World Health Organization (WHO) classification, 7 many extranodal diffuse large B-cell lymphomas have derived from a background of extranodal marginal zone lymphoma. [8][9][10][11] We found that a large subgroup of primary testicular diffuse large B-cell lymphoma has marginal zone lymphoma components, including small cell components and lymphoepithelial lesions. 12 Four mutually exclusive and apparently sitespecific, chromosomal translocations have been implicated in the development and progression of extranodal marginal zone lymphoma of mucosaassociated lymphoid tissue. These extranodal marginal zone lymphoma-associated translocations, t(11...

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T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10

Cited by 229 publications

References 47 publications

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

Immunoglobulin VH gene analysis in gastric MALT lymphomas

T(14;18)(q32;q21) involving MALT1 and IGH genes occurs in extranodal diffuse large B-cell lymphomas of the breast and testis

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