The T(11;18)(Q21;Q21) Chromosome Translocation Is a Frequent And

ICANCERRESEARCH57.3944-3948. September15. 19971 Advances in Brief

The t(11;18)(q21;q21) Chromosome Translocation Is a Frequent and Specific Aberration in Low-Grade but not High-Grade Malignant Non-Hodgkin's Lymphomas of the Mucosa-associated Lymphoid Tissue (MALT-) Type'

German Ott,2 Tiemo Katzenberger, Axel Greiner, Jorg Kalla, Andreas Rosenwald, Ute Heinrich, M. Michaela Ott, and Hans K. MÃ¼ller-Hermelink

Department of Pathology, University of WiArzburg, D-97080 Wurzburg, Germany

Abstract the MALT (4) suggests that these tumors, which may be of low- or high-grade malignancy, correspond to cells of postfollicular differen Primary extranodal malignant non-Hodgkin's lymphoma arising from tiation stages (5) and arise in a background of chronic inflammation the mucosa-associated lymphoid tissue (MALT-type lymphoma) repre. triggered by chronic infections or autoimmune processes (6). tents a subtype of B-cell lymphoid malignancies with distinct dlinicopath Few cytogenetic data have been published for this type of lym ological features and is often associated with a favorable prognosis. Unlike the situation In nodal non-Hodgkin's lymphoma ofB-cell lineage, few data phoma with a characteristic cytomorphology, immunophenotype, and are still available concerning the chromosomal constitution of MALT-type often indolent clinical behavior. In this paper, we present data from lymphomas. Until now, cytogenetic data from 29 low-grade MALT lym successful cytogenetic analyses of 44 cases of MALT-type NHLs phomas with karyotypic alterations have been reported from different arising in various extranodal sites, providing evidence that t(l 1; institutions, and virtually no data were available for high-grade MALT 18)(q21;q21) is a frequentand specificaberrationin MALT lympho type lymphomas. mas of low-grade malignancy but is not found in high-grade MALT We have analyzed the cytogenetics of 44 MALT lymphomas arising in type NHL. the stomach, parotid gland, thyroid gland, lung, breast, and conjunctiva. Clonal chromosome aberrations have been detected in 13 of 20 (65%) Materials and Methods low-grade and 20 of 24 (83%) high-grade tumors. More than half of the low-grade lymphomas with abnormal karyotypes (7 of 13 cases, 53%) Tissue Specimens. Tissues obtained for cytogenetic analyses were derived displayed clonal t(11;18)(q21;q21), thus specifically associating this traits from 44 fresh resection specimens (29 stomach, 6 thyroid, 4 salivary gland, 2 location with MALT-type lymphomas for the first time in a larger series. lung, 2 breast, and 1 conjunctiva) sent to the Department of Pathology. A part In contrast, t(11;18) was not found in a single case of 20 high-grade of the material was snap-frozen in liquid nitrogen, and blocks for histology MALT-type lymphomas with abnormal karyotypes, nor were transloca were fixed in 10% buffered formalin. tions t(14;18) or t(3;14), characterizing about 10â€”35% of primary nodal Histo1o@jrandImmunophenotyping. Histologicaldiagnoses were estab large cell lymphomas. Instead, these lymphomas were associated with lished on 5-,.@mparaffin sections from representative tissue blocks stained for t(8;14)(q24;q32) in three cases, frequent deletions in the long arm of H&E, Giemsa, periodic acid-Schiff, and Gomori's silver impregnation. Immu chromosome 6, and partial or whole gains of chromosomes 3, 7, 17, 18, nophenotyping on paraffin sections was performed using a modified peroxi and 21. date antiperoxidase technique after antigen retrieval by pressure cooking. The following antibodies were used: L26 (CD2O),CD3, antibodies against immu Introduction noglobulin light and heavy chains, the macrophage marker Ki-M1P, bcl-2, Specific genetic alterations acquired in a multistep process of BerH2 (CD3O),MIB1 (Ki67), and the pancytokeratin marker CAM5.2 (CK8/ 18). In addition, immunophenotypic studies were carried out on frozen sections transformation leading to the evolution of autonomous cell clones and using a panel ofmonoclonal antibodies directed against CD2, CD3, CD4, CD5, delineating particular disease entities are well recognized in nodal CD7, CD1O,CDI lc, CD23, CD3O,bcl-2, 1gM,IgD, IgA, IgG, ic,A,and Ki67. lymphoid malignancies of B-cell lineage. t( 14; l8)(q32;q2l ) is present Cytogenetic Analyses. Cell suspensions were obtained from the resection in 80â€”90% of follicular lymphomas and causes deregulation and specimens by pressing tumor tissues through a l00-,.@m nylon gauze under overexpression of the bcl-2 oncogene ( 1); t( I 1;l4)(q l3;q32) is a sterile conditions and collecting the cells in RPMI 1640 supplemented with characteristic chromosomal aberration in mantle cell lymphoma that 10%FCS and antibiotics.After washing several times, the cell numberwas involves the bcl-1/cyclin Dl gene in I 1q13 (2). More recently, t(3; adjusted to 1â€”2x I06/ml, and 10-mI cell cultures were directly harvested or l4)(q27;q32) or other translocations involving chromosomal band allowed to grow overnight. 3q27 have been associated with large B-cell lymphomas, the molec Ina partof thelow-gradelymphomas,thetumorcells werestimulatedusing ular equivalent of which is the deregulation of the bcl-6 oncogene (3). the CD4O system as described previously (7) and harvested after 3â€”5days. Briefly, lymphoma cell suspensions were depleted from macrophages, T cells, On the other hand, malignant NHLs3 arising in extranodal sites are and follicular center lymphocytes using magnetic beads coupled with either less well-characterized neoplasms on the cytogenetic and molecular anti-CD2, -CDI4 or -CD1O(Dynal, Hamburg, Germany) and further purified genetic level. The concept of primary extranodal NHL arising from by negative depletion using magnetic beads coated with antibodies to light and heavy chains not expressed by the lymphoma cells. The purity of cell suspen Received 7/7/97; accepted 7/30/97. sions obtained after magnetic bead depletion was between 95 and 99% B cells The costs of publication of this article were defrayed in part by the payment of page as calculated by three-color fluorescence-activated cell-sorting analysis (Bee charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. ton Dickinson, Mountain View, CA). Purified tumor B cells were cultured in @ Supported by the Deutsche Forsctiungsgemeinschaft. Sonderforschungsbereich 172. RPMI 1640 supplemented with gentamycin (1%), FCS (10%), transferrin (50 Teilprojekt C-8, and Sander-Stiftung Grant 94.025.2. @g/ml;Sigma),and 50 units/mI interleukin 4 (Genezyme, Rtisselsheim, Ocr 2 To whom requests for reprints should be addressed, at Pathologisches Institut der many) in culture flasks at a final volume of 10 ml. For CD4O antigen UniversitSt Wtlrzburg. Josef-Schneider-Striate 2, D-9708O Wurzburg, Germany. Phone: 49-(0)93 I-201 -3792; Fax: 49-(0)93 I-201-3440. activation, B cells were cultured in the presence of 0.1 @.tg/mlanti-CD4O

3 The abbreviations used are: NHL, non-Hodgkin's lymphoma; MALT, mucosa monoclonal antibody 89 (J. Banchereau, Schering-Plough, Dardilly, France) associated lymphoid tissue: ISH, in situ hybridization. presented by a mouse Ltk cell line stably transfected with CDw32 (8). 3944

lymphomasCaseAberrant TableI Resultsofcytogeneticanalysesin low-gradeMALT-type

metaphases/no.LocalizationKaryotypeanalyzedIStomach46,XY,t(l

1;l8Xq2l;q2l)13/212Stomach46,XY,t(ll;l8Xq2l;q2l)I 1/183Stomach46,XY,t(l 7/264Stomach46,XX,t(l I;18)(q21;q2I)I I)9/185Stomach48-5l,XY,+3,del(l I;I8)(q21;q2 l-3mar7/206Stomach46,XX,add(l8)(pl lXq2lq23),+ l8,+ I)10/287StomachNo I8StomachNo clonal aberration0/I aberration0/89StomachNo clonal aberration0/2710StomachNo clonal I1 clonal aberration0/I l;l8)(q2l;q2l)18/3312Lung46,XX,t(ll;l8Xq2l;q2l)15/27I1Lung46,XY,t(l

;q2l)24/2814Thyroid3Thyroid gland46,XY,t(l 1;I8)(q2l l;4)(q32;q27q32),del(3Xq26),add(3)(q25),+del(4)(q27q32),add(l0)(q22)10/1815Parotidgland46,XX,del(lXpl lp3l),ins( gland45,XX,â€”223/2716Parotid aberration0/2117ParotidglandNo clonal aberration0/3I glandNo clonal 319BreastNo8Parotid gland46,XX,dup(6@p22pter)10/I aberration0/1020Conjunctiva27-47,XX,+3[41,+clonal l0[2],+ l5[4l,â€”2I [3],â€”22[3J[cplJ7/Il

All cultures were pulsed with colchicine 30 mm before harvest. Metaphases cases without a low-grade lymphoma, clinical evidence that the site werepreparedaftersubjectingthecellstoa hypotonicsolutionofO.075MKCL affected was the only site or the main site of involvement (with or and fixation in a 3:1 solution of methanol-acetic glacial acid. The resulting without infiltration of regional lymph nodes) in combination with pellet was washed several times, droppedonto ethanol-cleanedglass slides, morphological indications of a primary extranodal origin. These in and stored for several days at room temperature. Chromosome banding was eluded a structure of the infiltrate consistent with a primary extranodal accomplished with a modified trypsin-Giemsa technique, and photomicro origin, the presence of abortive lymphoepithelial lesions, or alter graphs were constructed with a Zeiss Axiophot microscope (Zeiss, ations of surrounding, preserved tissues indicative of chronic inflam Oberkochen, Germany). All karyotypeswere describedaccordingto the InternationalSystem for mation often associated with the development of MALT-type NHL, HumanCytogeneticNomenclature(9).A karyotypicalterationwasregardedas such as Helicobacter pylon-associated gastritis, lymphocytic thyroid clonal if either two cells had the same structural aberration or chromosomal itis, or myoepithelial sialadenitis. gains or three cells showed the same chromosome loss. Cases without analyz able metaphases were not included. ISH studIes. Two-color ISH studies were performed from 14 low-grade Cytogenetic Analysis MALT-type lymphoma specimens that had also been processed for conven Low-Grade Lymphomas. Cytogenetic data of the 20 low-grade tional cytogenetic analysis. A biotinylated DNA probe specific for centromeric lymphomas are detailed in Table 1. Clonal chromosome aberrations sequences of chromosome 3 and a digoxigenin-labeled probe specific for chromosome 18 (Oncor, Gaithersburg, MD) were used according to the man were found in 13 samples (65%). Ten tumors presented with one ufacturer's instructions. Control specimens included reactive follicular hyper aberration only, and 7 cases (35%) were characterized by the recip plasias and tonsils. rocal translocation t( 11;18)(q2l ;q2l ; Fig. I). In all of these lympho mas arising in the stomach (n = 4), lung (n = 2), and thyroid (n = 1), Results t(l l;18) was the sole aberration. Chromosome band 11q21 was in Histological Diagnoses and Immunophenotyping volved in another case displaying del(l l)(q2lq23) with additional trisomies of chromosomes 3 and 18, but without structural alterations The 20 low-grade MALT-type NHLs included in the present study of chromosome 18. No further recurring structural aberrations or (10 stomach, 4 salivary gland, 2 lung, 2 thyroid, 1 breast, and 1 breakpoints could be observed. Trisomy 3 (+3) was present in two conjunctiva; Table 1) were composed of small-to-medium-sized cells lymphomas with additional karyotypic changes, and complex clones with a narrow or scant rim of sometimes pale cytoplasm and slightly (more than one aberration) were present in only three tumors (I 5%). irregular or round nuclei. Sometimes, a small number of transformed High-Grade Lymphomas. Clonal chromosomal aberrations were blast cells were also present. The infiltrate was prominent in the present in 20 of 24 cases analyzed (83%). With the exception of two marginal zone area of reactive follicular structures and/or spread out tumors (one displaying +7 and one with t(8;l4)(q24;q32) as the sole diffusely in the tissues involved, thereby forming characteristic lym aberrations), all high-grade lymphomas were characterized by highly phoepithelial lesions. No sheets of blasts were seen in any of the cases complex chromosome clones (Table 2; Fig. 2). The only recurrent classified as low-grade MALT-type lymphomas, and immunopheno reciprocal translocation encountered was t(8;l4)(q24;q32) in three typing revealed the characteristic immunophenotype of CD2O+, cases. Recurrent breakpoints were at l4q32 (10 cases), 6q23 (4 cases), CD22+, IgM+, IgDâ€”,CD5â€”, CDIOâ€”, and CD23â€”. In all but one and 1q32, 2p23, 3q21, 6q15, and 8q24 (3 cases each), among others. case, light chain restriction was demonstrated on frozen sections. The Whole or partial trisomies occurred for chromosome 3 in five cases, number of Ki67-positive cells ranged from 5â€”20%. chromosome 7 in four cases, chromosome 17 in five cases, chromo Twenty-four high-grade lymphomas of MALT type (19 stomach, 4 some 18 in three cases, and chromosome 2 1 in five cases. Frequent thyroid, and 1 breast; Table 2) on the other hand, showed sheets of losses of genetic material were observed in the long arm of chromo blast cells with a cytologic spectrum ranging from centroblasts to some 6 (nine cases). Translocation t(l 1;l8)(q2l ;q2l) was not found in immunoblasts or plasmablasts with high Ki67 indices (60â€”90%). a single case, nor were derivative chromosomes 11 or I8 resulting Classification of high-grade neoplasms as derived from MALT was from this translocation. based on either the presence of a concomitant low..grade component Interphase Cytogenetic Studies. Analysis of control specimens (simultaneous low-grade and high-grade lymphoma; n 7) or, in demonstrated two hybridization signals in an average of 95% of cells 3945

lymphoma?CaseAberrant Table 2 Results of cytogenetic analyses in high-grade MALT-type metaphases/no.LocalizationKaryotypeanalyzed21Stomach44â€”47,X,â€”X,t(2;l

I0,+mar10/1022Stomach6/623Stomach42â€”46,XY,del(7XqllXq3l;pl5),t(3;l4Xp23;q32),del(3)(q21).+der(3)t(3;3)(q2I;p26),â€” lq22),del(8@ql3),add(I4)(q32)X2,add(16)(q24)9/1024StomachNo aberration0/825Parotid clonal l;l6Xql4;q22)11/1126Stomach47,XX,+del(l)(plgland77â€”84(4n),XXXX,â€” 1,â€”l,+3,â€”6,â€”6,add(6)(ql5),â€”l3,â€”I6,der(l6)t(l 1J19/2027Stomach46,XY,+der(4)t(2;4Xq2l;q35),t(8;14Xq24;q32)7/1528Stomach44â€”48,XY,del(l)(q32),+3,dic(3;l4)(p21;q32),+del(6Xq23),+7,add(ll)[81/48,XX,+del(lXpl l),+3[I

lXq23),+ 10,â€”13,â€”14,â€”l5,+2- 4marllOJ/44â€”48,XY,del(lXq32)[4],dup(2)(pl5p2l),+3,dic(3;l4Xp2I; 1-5mar[12]22/2329StomachNo q32),â€”4,del(6Xq23),+7,â€”9,+add(IlXq23),â€”l3,+add(?2lXq22),+ aberration0/830Stomach68â€”89(4n),XXYY,+der(X)t(X;?X?;?),i(2XqlO),t(3;lO)(p2l;pl3),der(l0)t(3;I0)(p21;pl3),der(13)t(13;clonal

l4Xq33;q13),add(l4Xq32)[4XJ,+4-9mar8/831Parotid gland42â€”49,XX,+4,del(6Xql5q23),t(7;8)(q36;p2l),i(8XqlO),der(9)t(4;9)(q3l;q34),der(l4)t(?4;14)(?pl0;ql0),+ 18, 3)6/932Stomach42-46,XY,t(8;14Xq24;q32)10/1433Parotidder( l9)t( 17; l9)(q2l ;ql

gland47,XX,+77/1434Pat-odd gland63â€”99(4n),XXXX,â€”X[4],del(2Xp23)X2,t(3;9)(q2l;p24)X2,+6[4],+7[2],+7X2[2],+8[21,der(l l)t(I :1l)(p32; 17(2]6/835Stomach39-.43,XX,inv(l)(p36q25),add(6Xq2l),add(8)(p2l),9qh+,add(lq25),der( 1l)t( 1;11)(p32;q25)[4],+ I7,+ lXq23),add(13)(q22),add(l5)(pl3),â€”17, add(l8)(q23)4/1936StomachNo aberration0/1537Stomach47â€”49,XX,del(6)(q22),+clonal l2,t(l4;l6Xq32;q22),+2l4/438Breast46-48,XX,+X,add(l)(ql l8[2],â€”2l[3],+mar6/939Stomach45â€”49,XY,+5,+ 1),+3,â€”7,add(l4)(q32),+ l),+21[3]31/4840StomachNo I2,+2l[28]/50,XY,+5,+ 12,+del(l7)(pl aberration0/441Stomach43â€”49,XY,+X,dup(7Xqlclonal 1q32),9qh+,+ l-2mar[5]/33-48,XY,+X,del(l)(pl l),der(3)t(1;3)(q3l;p26), lql2)[5]10/2642Stomach43â€”48,XY,t(2;l4)(q2l;q32),del(6@q2lq23),del(7Xq22),add(l8)(pl9qh+,+dup(I7)(ql l),i(21)(qlO)[81/44-48,XY,t(2;l4Xq2l;q32), 18,i(2l)(qlO)[2]10/1443Stomach4lâ€”46,XY,?del(2Xp23),der(l8)t(6;l8Xq22;q23),i(2l)(qIO),der(2l)t(1del(6)(q21q23),del(7)(q22),+ l;q13)9/944 l;2l)(ql2;q22),t(20;22)(ql 33-46,XY,del(6)(q15q23),dup(l7Xql 1q21) a Cases2Stomach1-37, primary high grade lymphomas; cases 38-44, mixed low- and high-grade tumors.14/14

for both probes. Nuclei with three signals were observed in lymphomas of MALT type as defined in the revised European 0.6 Â±0.3% of cells (mean Â±1 SD). Therefore, the finding of three American lymphoma (REAL) classification (10), and for the first signals in 3% or more of cells was considered to indicate a trisomy. time, cytogenetic data on high-grade MALT-type NHL are presented. Only 1 of 14 cases analyzed, however, was positive for both trisomy Of 20 low-grade tumors studied, 13 (65%) were found to be 3 and trisomy 18, and this case had also been found to harbor a +3 characterized by karyotypic alterations. In 7 of 13 (53%) lymphomas and a + 18 in conventional cytogenetic analysis (case 5). All other with an abnormal chromosome constitution, a clonal t(ll;18)(q2l; cases failed to show aneusomic chromosome clones by ISH. q21) translocation could be demonstrated (Fig. 1). This rearrangement .. was first described by Levine et a!. (1 1) in two small lymphocytic Dtscussion ... lymphomas arising in the stomach and the lacnmal gland; subse The present study constitutes the largest series available to date quently, four more cases have been reported and classified either as concerning cytogenetic alterations in extranodal marginal zone B-cell MALT-type lymphoma (12), small lymphocytic lymphomas with Ii ii I@ U U

@ @oU H U z: Fig. l.Akai-yotypefromalow-gradeMALT-typelymphoma 6 7 8 9 10 / ii 12 of the thyroid (case 13) illustrating t(I I;18)(q2l ;q2l ) as the sole aberration. Rearranged chromosomes 11 and 18 are marked by arrows. S. a@$.@ a4 h@ 13 14 15 16 17 f 18

19 20 21 22

3946

@ (F@â€”!1 1@1 II 4 5

II 1@I Fig. 2. Chromosome analysis of a high-grade gastric MALT-type lymphoma (case 42) showing 47,XY,t(2; 8 l4Xq2l;q32),del(6Xq2lq23),del(7)(q22),+l8,i(2l)(qlO). Rearranged chromosomes are marked by arrows. II I, II U 1.11 13 @1.4 15 16 17 18

,a*@a.19202122 I. xY

prominent extranodal involvement (13), or diffuse small B-cell lym that the tumors in our series represented early stages and that trisomy phoma with features of MALT (14). Interestingly, in all these cases, 3 might be a factor associated with progression rather than tumori as well as in our series, t(l l;18) was the only aberration. In the case genesis. Vice versa, the evolution of t(l 1;18) may delineate tumors reported by Horsman et a!. (12), an additional aberrant, unrelated characterized by a high grade of karyotypic stability, which is sug clone could be observed with trisomy 3 in three cells. gested by its sole occurrence in all 13 cases reported so far (including All cases in our series presented with primary mucosal involve our present cases). Although having been found in lymphomas in ment, cytomorphological features, and an immunophenotype charac advanced stages (1 1, 14), the tumors were always described as com teristic of MALT-type lymphoma. We were able, therefore, in agree posed exclusively of small cells, as they were in our series, without ment with and confirming previous reports, to strongly associate significant admixture of blast cells. In contrast, some of the cases t(ll;18) to extranodal low-grade marginal B-cell lymphoma of MALT reported by Dierlamm et a!. (23) showed very complex karyotypic type. alterations (including a high +3 rate) and were cytomorphologically The molecular genetic equivalent of t(ll;l8)(q21;21), however, is described as tumors with a significant admixture oflarge or blast cells. not clear, nor are the genes known to be involved in this translocation. The concept of t(l l;l8) characterizing tumors without cytological Several candidate (onco)genes are known to be localized in l8q2l, transition to large cell morphology is further strengthened by the fact including the DCC gene (15), the YES proto-oncogene (16), JTF2 that we were not able to detect this translocation in mixed/simultane (17), the SSAV-relatedendogenousretroviralelement(18), and the ous low- and high-grade tumors or in primary high-grade MALT-type DPC4 gene (19). Interestingly, allele imbalances at the DCC locus lymphomas. Although it cannot be completely ruled out that the have recently been found in two gastric low-grade MALT-type NHLs translocation was lost in t(1 l;18)-positive lymphomas during tumor (20). No rearrangements of the bcl-2 gene localized in l8q21 have progression to high-grade lymphomas, the complete absence of been demonstrated in MALT lymphomas (21â€”23)or in cases cytoge der(l 1) or der(18) marker chromosomes in any of the cases studied netically positive for t(ll;18) (12â€”14). does argue strongly against this possibility. Our data suggest that t(l l;18) is a frequent change in low-grade This report details for the first time cytogenetic data on a large MALT-type NHLs being found in 35% of the cases (and in >50% of series of extranodal high-grade lymphomas of MALT type. The only cases with aberrant karyotypes). It is not clear, however, why previous recurrent structural aberration found in our series of 24 cases studied reports on cytogenetic investigations in MALT lymphomas failed to was t(8;l4)(q24;q32) involving the c-myc locus in 8q24 in 3 primary detect the translocation (22â€”24).In contrast, these reports stated the high-grade tumors. Rearrangements of c-myc have been demonstrated association of a trisomy 3 to MALT-type lymphomas in high frequen in 50% of gastric primary high-grade lymphomas in a study by van cies of up to 60%. These data were further confirmed by ISH studies Krieken et al. (28). Because the t(8;14)/c-myc rearrangement is an using centromere-specific repetitive DNA probes revealing a +3 in infrequent finding in nodal non-Burkitt's high-grade lymphomas (29), 60â€”85%ofcases (25â€”27).Inour series, however, an additional cytogenetic or molecular genetic alterations involving the deregula chromosome 3 was detected in only two lymphomas (10%). Addi tion of c-myc might be important factors in extranodal high-grade tional interphase cytogenetic studies of 14 of the low-grade cases with malignancies. In addition, we have observed t(8;l4) in two additional centromere-specific probes for chromosomes 3 and 18 revealed cells primary extranodal high-grade non-Burkiu's lymphomas arising in with additional copies of these chromosomes in only 1 case that had the small intestine and the paranasal sinus, respectively, but in only 1 also been positive in banding studies. of 53 nodal large cell lymphomas (data not shown). With the exception of the majority of the 9 cases reported by Recurrent chromosome alterations encountered in our high-grade Wotherspoon et a!. (24), the finding of a +3 in the other reports was MALT lymphomas were, among others, structural aberrations involv always associated with complex karyotypic alterations (22, 23), in ing l4q32 and several breakpoints in 6q as well as partial or whole contrast to our series, in which only 3 of 13 lymphomas were char trisomies for chromosomes 3, 7, 17, 18, and 21 and recurrent deletions acterized by more than 1 aberration. Because complex chromosome in 6q (Table 2), all occurring in primary as well as in simultaneous alterations are commonly present in either advanced stages of low low- and high-grade lymphomas. The t(1 1;18)(q2 1;q2l) translocation grade or high-grade lymphoid tumors, this difference might indicate was not found. Deletions in chromosome region 6q and structural 3947

Downloaded from cancerres.aacrjournals.org on September 28, 2021. © 1997 American Association for Cancer Research. CYTOGENETIC ANALYSIS OF MALT-TYPE LYMPHOMAS aberrations involving l4q32 as well as gains ofchromosomes 3, 7, 12, 12. Horsman, D., Gascoyne, R., Klasa, R., and Coupland, R. t(11;l8Xq2I ;q2l. 1): a 18, and 21 are frequent findings in nodal high-grade lymphomas (29). recurring translocation in lymphomas of mucosa-associated Iymphoid tissue (MALT)? Genes Chromosomes Cancer, 4: 183-187, 1992. High-grade lymphomas of MALT type, therefore, do not seem to 13. Griffin, C. A., Zehnbauer, B. A., Beschorner, W. E., Ambinder, R., and Mann, R. differ to a significant extent from nodal high-grade tumors with regard t(l l;l8)(q21;q2l) is a recurrent chromosome abnormality in small lymphocytic lymphoma. Genes Chromosomes Cancer, 4: 153-157, 1992. to their genetic constitution, with two important exceptions: (a) t(14; 14. Leroux, D., SeitÃ©,P.,Hillion, J., Le Marc'hadour, F., PÃ©gouriÃ©-Bandelier,B.,Jacob, 18)(q32;q2l) has been reported to occur in 20â€”30%of nodal diffuse M.C., Larsen,C.J., andSono,J. J. t(I l;I8Xq2I;q2l)maydelineatea spectrumof large cell lymphomas but was absent in all our cases studied; and (b) diffuse small B-cell lymphoma with extranodal involvement Genes Chromosomes Cancer,7: 54â€”56,1993. no t(3;l4)(q27;q32) or other aberrations involving the locus of the 15. Fearon, E. R., Cho, K. R., Nigro, J. M., Kem, S. E., Simons, J. W., Ruppert, J. M., bcl-6 oncogene in 3q27 could be observed. This finding might be of Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., and Vogelstein, B. particular interest, because Offit et al. (30) described rearrangements Identification of a chromosome l8q gene that is altered in colorectal cancers. Science (Washington DC), 247: 49-56, 1990. of bcl-6 in a high proportion of cases with extranodal involvement and 16. Ohno, H., Fukuhara, S., Takahashi, R., Mihara, K. I., Sugiyama, T., Doi, S., Uchino, comparatively favorable prognosis; it was not clear, however, whether H., and Toyoshima, K. c-yes and bcl-2 genes located in 18q21.3 in a follicular a part of these cases represented true extranodal lymphomas or merely lymphoma cell line carrying a t(l4;l8) chromosomal translocation. mt. i. Cancer, 39: 785â€”788,1987. nodal tumors with extensive extranodal involvement. Only a part of 17. Henthom, P., Kildedjian, M., and Kadesch, T. Two distinct transcription factors that rearrangements involving bcl..6 are visible on the cytogenetic level bind the immunoglobulin enhancer p.E5/kE2 motif. Science (Washington DC), 247: 467â€”470,1990. (31); therefore, the association of bcl-6 rearrangements with high 18. Brack-Wemer, R., Barton, D. E., Werner, T., Foellmer, B. E., Leib-MOsch, C., grade MALT-type lymphomas will have to await additional molecular Francke, U., Erfie, V., and Hehlmann, R. Human SSAV-related endogenous retroviral genetic studies that are currently under way. element: LTR-like sequence and chromosomal localization to l8q2l . Genomics, 4: 68â€”75,1989. 19. Hahn,S. A.,Schutte,M.,ShamsulHoque,A.T. M.,Moskaluk,C.A.,da Costa,L, Acknowledgments Rozenblum, E., Weinstein, C. L., Fischer, A., Yen, C. J., Hruban, R. H., and Kem, S. E. DPC4,a candidatetumorsuppressorgeneat humanchromosomel8q21.l. The expert technical assistance of H. Bruckner, C. Gartner, A. Science(WashingtonDC),271:350â€”353,1996. Trumpfheller, and M. Reichert is gratefully acknowledged. We also thank E. 20. Calvert, R., Randerson, J., Evans, P., Cawkwell, L., Lewis, F., Dixon, M. F., Jack, A., Schmitt for artful photographic work. We are indebted to Prof. G. Bussolati Owen,R.,Shiach,C.,andMorgan,G.J. Geneticabnormalitiesduringtransitionfrom Helicobacter-associatedgastritisto low-grade MALToma. Lancet, 345: 26â€”27,1995. (University of Torino, Italy) for providing one of the specimens. 21. 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Downloaded from cancerres.aacrjournals.org on September 28, 2021. © 1997 American Association for Cancer Research. The t(11;18)(q21;q21) Chromosome Translocation Is a Frequent and Specific Aberration in Low-Grade but not High-Grade Malignant Non-Hodgkin's Lymphomas of the Mucosa-associated Lymphoid Tissue (MALT-) Type

German Ott, Tiemo Katzenberger, Axel Greiner, et al.

Cancer Res 1997;57:3944-3948.

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