T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma

Abstract

The three chromosomal translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32) are associated with MALT lymphoma. In a case of MALT lymphoma of the thyroid, we observed t(3;14)(p14.1;q32) by cytogenetic analysis. Fluorescence in situ hybridization studies showed that the immunoglobulin heavy chain locus (IGH) was rearranged on chromosome 14. Long-distance inverse polymerase chain reaction identified FOXP1 as the partner gene on chromosome 3. To determine the frequency of the t(3;14)(p14.1;q32), two fluorescence in situ hybridization assays were established to screen 91 MALT lymphomas, all of which were negative for the above-mentioned three translocations, and eight splenic and six nodal marginal zone lymphomas. Overall, nine MALT lymphomas (10%) harbored t(3;14)(p14.1;q32) comprising tumors of the thyroid (three of six), ocular adnexa (four of 20), and skin (two of 20), whereas those of the stomach (n = 20), salivary gland (n = 20), and lung (n = 5) were negative as well as the splenic and nodal marginal zone lymphomas. Most t(3;14)(p14.1;q32) + MALT lymphomas harbored additional genetic abnormalities, such as trisomy 3. Further studies revealed that the three known translocations and t(3;14)(p14.1;q32) are mutually exclusive. Real-time quantitative reverse transcriptase polymerase chain reaction showed upregulation of FOXP1 in cases with t(3;14)(p14.1;q32) or trisomy 3. This study identifies FOXP1 as a new translocation partner of IGH in a site-dependent subset of MALT lymphomas.

Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1α expression

“…Nuclear FOXP1 expression was associated significantly with the expression of ER-a and marginally with PgR expression as previously reported in breast cancer by Fox et al 8 However, this group observed no direct regulation of FOXP1 expression levels by estrogen in experiments with the ERpositive MCF-7 cell line. This is interesting in the context of the fluctuations of FOXP1 expression in the normal endometrium, as these would normally indicate that its expression was hormonally regulated.…”

“…4 Although the role of this protein in human cancer development and progression remains obscure, recent clinicopathological studies reported an important role in B-cell lymphomas. [6][7][8] A role for FOXP1 as a tumor suppressor gene in the development of breast cancer has been also suggested. 9 Studies of FOXP1 knockout mice have recently demonstrated that this molecule plays an essential role in development and that its deletion results in an embryonic lethal phenotype 10 Interestingly, a loss of FOXP1 expression in cardiac myocytes results in their increased proliferation while loss of FOXP1 in cushion mesenchyme of heart outflow tracts was associated with decreased apoptosis, both observations are consistent with a role for FOXP1 as a tumor suppressor gene where loss of expression could potentially increase proliferation and reduce programmed cell death.…”

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

“…In this study, we have not assayed the presence of the recently described t(3;14)(p14.1;q32). 11 Another critical point in the pathogenesis of MALT lymphomas is the potential role of aberrant nuclear expression of bcl10. Under physiological conditions bcl10 plays a dual pro-and antiapoptotic role.…”

“…9,10 Nevertheless, there is increasing evidence to suggest that cases diagnosed with MALT lymphomas arising at different sites differ in the presence of infectious specific antigens-Helicobacter, Campylobacter, Borrelia, Chlamydia-promoting lymphoid cell proliferation, and in the frequency of chromosomal translocations such as t(11;18)(q21;q21), or the newly described t(14;18)(q32;q21) and t(3;14) (p14.1;q32). [10][11][12] As in the case of other extranodal lymphomas, most MALT lymphomas arising in the ocular adnexa have an indolent course with a favorable prognosis; 1,2 previous reports have demonstrated low local aggressivity with a reasonably good possibility of relapse control by radiotherapy. 13 This is in keeping with the findings from a large series of MALT lymphomas, which showed that the efficacy of treatment varied accordingly with the site, stage, and clinical status of patients.…”

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

“…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.…”