Ossifying fibromyxoid tumor of soft parts. Cytogenetic findings

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently described, rare but morphologically distinctive soft tissue tumor. The histogenesis of this lesion remains uncertain, although several immunohistochemical and ultrastructural features suggest that it is an unusual neural tumor, possibly of Schwann cell origin. We report here a case of a malignant variant of OFMT that occurred in the foot of a 52-year-old man. The karyotype of a pulmonary metastasis exhibited the following complex numeric and structural aberrations:72 approximately 74,XXY,-5,+6,+del(8)(p21),del(9)(p22),+10,der(11)t(3;11)(p21;p15),del(12) (q13),der(13)t(5;13)(q13;q34),+18,+19,+20,-22 [cp10]. A kidney metastasis exhibited the following karyotypic abnormalities: 46,XY,add(3)(p11),+der(3)t(3;?;11)(3qter-->3p11::?::11q13-->11qter), -5,del(8)(p21),add(9)(q22),del(9)(p22),der(11)t(3;11)(p21;p15),del(12)(q13),+der(13)t(5;13) (q13;q34),-22. To our knowledge, this is the first reported case of OFMT in which clonal chromosomal aberrations have been shown.     

Different clones of t(1;12)/t(12;12) involving the ETV6 gene in a case of acute myeloid leukemia

We report a boy with Down syndrome and leukemia who acquired uniparental isodisomy of chromosome 7q as a secondary chromosomal change during recurrence of the disease. His karyotype before therapy was 46,XY,der(1)t(1;1)(p36;q32),-7,+21c/46,idem,del(9)(p22), whereas at recurrence it was 46,XY,der(1)t(1;1)(p36;q32,-7,der(7)(qter-->p22 through pter::q10-->qter),del(9)(p22),+21c/47,XY,+21c. By using polymerase chain reaction amplification of D7S493 and D7S527 markers, we identified the loss of the maternal chromosome 7 with a consequent paternal isodisomy in the clone with dup7q. This rearrangement could be implicated in the progression of the disease by causing (1) nullisomy for a gene or genes located on 7p22-->pter, (2) functional double doses of exclusively paternal expressed genes, and (3) restoration of the effects produced by haploinsufficiency of biparental expressed genes.     

Molecular cytogenetic characterization of human papillomavirus16-transformed foreskin keratinocyte cell line 16-MT

Anogenital cancers are closely associated with human papillomavirus (HPV), and HPV-infected individuals, particularly those with high-grade dysplasias, are at increased risk for cervical and anal cancers. Although genomic instability has been documented in HPV-infected keratinocytes, the full spectrum of genetic changes in HPV-associated lesions has not been fully defined. To address this, we examined an HPV16-transformed foreskin keratinocyte cell line, 16-MT, by GTG-banding, spectral karyotyping (SKY), and array comparative genomic hybridization (array CGH); these analyses revealed multiple numerical, complex, and cryptic chromosome rearrangements. Based on GTG-banding, the 16-MT karyotype was interpreted as 78-83,XXY,+add(1)(p36.3),+3,+4,+5,+5,+7,+8,+i(8)(q10)x2,+10,?der(12),der(13;14)(q10;q10),+15,+16,add(19)(q13.3),+21,+21,-22[cp20]. Multicolor analysis by SKY confirmed and further characterized the anomalies identified by GTG banding. The add(1) was identified as a der(1)(1qter-->1q25::1p36.1-->1qter), the add(19) as a dup(19), and the der(12) interpreted as a der(11) involving a duplication of chromosome 11 material and rearrangement with chromosome 19. In addition, previously unidentified der(9)t(9;22), der(3)t(3;19), and der(4)t(4;9) were noted. The 16-MT cell line showed losses and gains of DNA due to unbalanced translocations and complex rearrangements of regions containing known tumor suppressor genes. Chromosomal changes in these regions might explain the increased risk of cancer associated with HPV. Also, array CGH detected copy-number gains or amplifications of chromosomes 2, 8, 10, and 11 and deletions of chromosomes 3, 4, 11, and 15. These results provide the basis for the identification of candidate oncogenes responsible for cervical and anal cancer in amplified regions, and for putative tumor suppressor genes in commonly deleted regions like 11q22-23. Furthermore, these data represent the first full characterization of the HPV-positive cell line 16-MT.     

Identification of de novo chromosome rearrangements: five cases analyzed with differential chromosome painting

We report on five cases of de novo structural chromosome rearrangements that were difficult to identify by conventional G-banding analysis. In all five cases, differential chromosome painting (DCP) provided evidence for the presence of an additional segment and its origin. A combination of DCP with subsequent conventional fluorescence in situ hybridization (FISH) analysis using adequate locus-specific probes and reexamination of G-banding patterns resulted in successful identification of the rearrangements. Their karyotypes were finally interpreted as 46,XY,der(1)(qter --> q42.1::p36.3 --> qter) in case 1; 46,XY,der(8)(8pter -->8q24.3::8q24.3 --> 8q23.2::?p11.2 --> ?ps) in case 2; 47,XY,+der(10)(pter --> q11) in case 3; 46,XX,der(3)(17pter --> 17p11.2::3p26 --> 3qter) in case 4; and 46,XY,dup(1) (pter --> q32::q25 --> qter) in case 5.     

FISH analysis of MALT lymphoma-specific translocations and aneuploidy in primary cutaneous marginal zone lymphoma

Primary cutaneous marginal zone lymphomas (PCMZL) share histological and clinical characteristics with mucosa-associated lymphoid tissue (MALT) lymphomas suggesting a common pathogenesis. A number of recurrent structural and numerical chromosomal aberrations have been described in MALT lymphoma, but their incidence in PCMZL is largely unknown, as is their relation with clinical and pathological data. In this study, the incidence of t(11;18)(q21;q21), t(1;14)(p22;q32), two different t(14;18)(q32;q21), involving either IGH/MALT1 or IGH/BCL2, and numerical aberrations of chromosomes 3, 7, 12 and 18 were analysed in 12 patients with PCMZL, with follow-up of up to 10 years. Nuclei were isolated from paraffin wax sections for dual-colour interphase fluorescence in situ hybridization (FISH) using various probe sets either flanking or spanning the involved genes. T(14;18)(q32;q21), with breakpoints in IGH and MALT1, was found in three cases. All three had partly monocytoid histological appearances and lacked blastic transformation. An additional trisomy of chromosome 3 was detected in one of these cases. Trisomy 18 was present in two lymphomas without monocytoid morphology. No definite correlation was seen with any clinical feature, including Borrelia serology. Neither t(11;18)(q21;q21), nor t(1;14)(p22;q32) or any other translocation involving IGH, BCL10, MALT1, BCL2 and API2, amplification or deletion of chromosomal region 11q21, 18q21, 1p22, and 14q32 was detected. These results indicate that a subgroup of PCMZL with partly monocytoid morphology is genetically related to MZL at other extranodal sites.     

Variant t(14;18) in malignant lymphoma: a report of seven cases

The BCL2 gene was identified through molecular analysis of the breakpoints involved in the t(14;18)(q32;q21) found in the majority of follicular lymphomas (FL). Variant translocations leading to juxtaposing of the BCL2 with either the IGK or IGL gene have been recognized in B-cell malignant lymphoma, although they are rare. We identified seven lymphoma cases that had variant translocations. Three cases had simple translocations involving two chromosomal regions: t(18;22)(q21;q11.2) in two cases and t(2;18)(p11.2;q21) in the third case. Complex translocations affecting more than two chromosomes were seen in the remaining four cases. Fluorescence in situ hybridization using the LSI IGH/BCL2 DNA probes revealed rearrangements of the BCL2 gene locus in all cases. In addition, expression of BCL2 protein was seen in all cases; only five of the seven cases expressed BCL6 protein. Morphologically, the lymphomas were categorized as B-cell follicular lymphoma in six cases and in the seventh case as diffuse large cell lymphoma (Richter syndrome) transformed from preexisting chronic lymphocytic leukemia (CLL). In case 2, the variant t(18;22) was seen as a secondary aberration evolving from a trisomy 12 clone. The findings revealed that BCL2 rearrangements in some malignant lymphomas occur through variant simple or complex chromosomal translocations, but always involving the IGH, IGK, or IGL chromosomal site. In addition, fluorescence in situ hybridization proved to be an important tool in evaluating these cases by showing IGH/BCL2 gene fusion or repositioning of the BCL2 gene.     

Clonal chromosome aberrations in a keratoacanthoma and a basal cell papilloma

Clonal chromosome abnormalities were found in short-term cultures from two epithelial skin tumors, a basal cell papilloma and a keratoacanthoma. The three-way translocation t(2;6;11)(q21;q27;p13) was the sole clonal rearrangement in the basal cell papilloma. The karyotype of the keratoacanthoma was more complex: 46,XX,der(2)(2pter----2p13::2p11----cen----2q37: :5q33----5qter),der(2) (:2p13----cen----2q37::6q23----6qter),der(5)t(2; 7;5)(q37;q11;q33),der(6) (6pter----cen----6q23::2p13----2pter),der(7)t(2; 7;5)(q37;q11;q33), del(13)(q11q14). In addition, several nonclonal structural changes were seen in both tumors.     

Cytogenetic and molecular studies in patients with chronic myeloid leukemia and variant Philadelphia translocations

Out of 105 Philadelphia (Ph) positive chronic myeloid leukemia patients analyzed, six (5.7%) carried a variant Ph translocation, namely t(6;9;9;10;22)(q24;p13;q34;p15;q11); t(9;13;22)(q34;q21;q11);der(2)(2pter----2q31::9q21---- 9q34::22q11----22qter) and der(9)t(2;9) (9pter----9q21::2q31----2qter);t(7;9;22)(q11;q34 ;q11), 14q + ;t(7;9;22)(q35;q34;q11), and t(9;11;22) (q34;q13;q11), respectively. Five of these patients were analyzed with Southern blotting. Three of them showed an atypical molecular pattern; namely, the patient with t(9;13;22) showed no rearrangement in the breakpoint cluster region (bcr), the patient with t(7;9;22)(q35;q34;q11) showed a 3' deletion, and the patient with t(7;9;22), 14q + showed a bcr rearrangement 3' to the exon 4 of the M-BCR. Chromosome in situ hybridization studies demonstrated that in patient one, a two-step translocation occurred: the first step moved the 3' bcr from chromosome 22 to chromosome 9, and the second moved the terminal part of 22q, carrying the c-sis protooncogene, to 10p. Variant Ph translocations appear to be associated with atypical molecular breakpoints.     

Derivative (3)t(3;18)(q27;q21)t(18;16)(q21;?) involving the BCL2 and BCL6 genes in follicular lymphoma with t(3;14;18)(q27;q32;q21)

Follicular lymphoma (FL) is genetically characterized by t(14;18)(q32;q21) involving the BCL2 gene (BCL2), and is often associated with 3q27 translocations involving the BCL6 gene (BCL6). We describe here an unusual case of FL with a variant three-way translocation t(3;14;18)(q27;q32;q21). A 57-year-old man was given a diagnosis of FL, grade 2. Chromosome analysis showed 49,XY,+X,+3,t(3;14;18)(q27;q32;q21),i(6)(p10),+21. Spectral karyotyping confirmed three derivative chromosomes, der(3)t(3;18)(q27;q21), der(14)t(3;14)(q27;q32), and der(18)t(14;18)(q32;q21). Furthermore, an extra chromosome 3 was shown to be an unbalanced translocation der(3)t(3;16)(q27;?). Fluorescence in situ hybridization (FISH) analyses detected an IGH/BCL2 fusion signal on the der(18)t(14;18)(q32;q21). FISH also demonstrated split signals of BCL2 and BCL6 on both the der(3)t(3;16)(q27;?) and the der(3)t(3;18)(q27;q21). The findings indicate that the three-way translocation involved BCL2, IGH, and BCL6 and that the der(3)t(3;16)(q27;?) contained the 18q21 fragment including BCL2. It is probable that the translocation between chromosome 16 and the der(3)t(3;18)(q27;q21) occurred after duplication of the der(3)t(3;18)(q27;q21) as clonal evolution. Thus, this additional chromosome was revised as der(3)t(3;18)(q27;q21)t(18;16)(q21;?) and the final karyotype was as follows: 49,XY,+X,t(3;14;18)(q27;q32;q21),+der(3)t(3;18)(q27;q21)t(18;16)(q21;?),i(6)(p10),+21. These findings suggest that the der(3)t(3;18)(q27;q21) involving BCL2 and BCL6 had a crucial role in the pathogenesis of FL with t(3;14;18)(q27;q32;q21).     

Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of adult non-Hodgkin lymphoma (NHL), is infrequently seen in adolescents and is rare in children. Due to the infrequency of the disease, single institution-based cytogenetic and fluorescence in situ hybridization (FISH) studies of pediatric DLBCL have not been reported so far and, hence, the possible differences in pediatric and adult DLBCL have not been evaluated. We performed cytogenetic and FISH analyses of 7 pediatric and 5 young adult DLBCL cases referred to the University of Nebraska Medical Center. Karyotypic studies revealed numeric and structural chromosome abnormalities in all cases. Loss of chromosomes 2, 3, 4, 6, 12, 15, 16, and 17, and gain of 12, 18, and X were observed in more than 20% of the cases (#10878;3 cases). Sex chromosome abnormalities and cytogenetically unidentifiable chromosomes and/or segments were observed in 80% (10/12) of the cases. Recurrent breakpoints (observed in 3 or more cases) included 14q32 (IGH) and 17p13 (TP53), which clustered in the young adult group. The breakpoints 7q36, 9p24, 13q34, and 16q24 were noted in two cases each. We performed interphase FISH studies to verify the possible rearrangements of the breakpoints that are frequently implicated in adult DLBCL. Our results confirmed that the pediatric cases did not show rearrangements of 3q27 (BCL6), 14q32 (IGH), 18q21 (BCL2), 8q24 (CMYC), and 17p13 (TP53), except for one case with IGH;BCL2 dual fusion [t(14;18)(q32;q21)] and one with a 17p13 (TP53) deletion. Although 3q27 was noted to be rearranged by conventional cytogenetics in two young adult DLBCL cases, FISH investigations verified that BCL6 was not disrupted. The t(8;14)(q24;q32) with rearranged CMYC ascertained by FISH, was observed in a single young adult DLBCL case. These results highlight a distinctly different representation of cytogenetic abnormalities in pediatric versus adult DLBCL.     

Molecular cytogenetic study of a mantle cell lymphoma with a complex translocation involving the CCND1 (11q13) region

We describe a progressive mantle cell lymphoma (MCL) in which multicolor fluorescence in situ hybridization (M-FISH) on metaphases did not detect the characteristic t(11;14)(q13;q32), although translocations of chromosomes 11 with 15, and 14 with 15 were observed. When CCND1/IGH probes were hybridized to metaphases, however, cryptic fusion signals were detected on the der(11) and der(14) sites of CCND1 (11q13) and IGH (14q32), revealing a complex translocation involving chromosomes 11, 14, and 15. Interphase FISH with CCND1/IGH probes revealed varying patterns with one or two fusion signals, and some with no clear evidence of fusion. Loss of 17p and gain of 3q, known to be associated with disease progression in MCL, were detected with M-FISH and confirmed with the use of p53 and BCL6 probes together with comparative genomic hybridization, which detected also an interstitial deletion on 7p21. This case further illustrates the value of M-FISH in combination with fusion probes in elucidating complex cytogenetic abnormalities.     

Multiple apparently unrelated clonal chromosome abnormalities in a squamous cell carcinoma of the tongue

We have cytogenetically examined short-term cultures from a squamous cell carcinoma of the tongue, a tumor type in which chromosome aberrations hitherto have not been reported. No less than 12 pseudodiploid clones were detected, giving the tumor karyotype 46,X,der(X)t(X;1)(q26;p32),der(1)(Xqter→Xq26::1p32→cen→1q42:),del(13)(q11q21),t(15;?) (q26;?)/46,XX,t(1;?)(p34;?),inv(2)(p21q11)/46,XX,t(1;10)(p32;q24)/46,XX,+der(1)(12pter→ 12p11::1p11→cen→1q32::11q13→11q32→1q42:),del(11)(q13q22), - 12, der(17)t(1:17) (q42;p13)/46,XX,inv(1)(p22q44)/47,XX,del(1)(q32),der(17)t(1:17)(p22;q25),der(1)inv(1) (q25q44)t(1;17)(p22;q25),ins(14;7)(q11;q22q36), + 14/46,XX,t(1;4)(q23;q35)/46,XX,t(1;21) (q25;q22),t(2;10)(q31;q26),t(22;?)(q12;?)/46,XX,del(1)(q32)/46,XX,t(1;8)(q44;q21)/46,XX, t(2;21)(q11;p11)/46,XX,t(9;11)(q34;q13). The large number of apparently unrelated abnormalities leads us to suggest that the carcinoma may have been of multiclonal origin.     

Cytogenetic,spectral karyotyping,fluorescence in situ hybridization,and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions,and MYC and MLL amplification

Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.     

MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression

Mucosa-associated lymphoid tissue (MALT) lymphoma is specifically associated with t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21). t(11;18)(q21;q21) fuses the N-terminus of the API2 gene to the C-terminus of the MALT1 gene and generates a functional API2-MALT1 product. t(1;14)(p22;q32) and t(14;18)(q32;q21) bring the BCL10 and MALT1 genes respectively to the IGH locus and deregulate their expression. The oncogenic activity of the three chromosomal translocations is linked by the physiological role of BCL10 and MALT1 in antigen receptor-mediated NFkappaB activation. In this study, MALT1 and BCL10 expression was examined in normal lymphoid tissues and 423 cases of MALT lymphoma from eight sites, and their expression was correlated with the above translocations, which were detected by molecular and molecular cytogenetic methods. In normal B-cell follicles, both MALT1 and BCL10 were expressed predominantly in the cytoplasm, high in centroblasts, moderate in centrocytes and weak/negative in mantle zone B-cells. In MALT lymphoma, MALT1 and BCL10 expression varied among cases with different chromosomal translocations. In 9/9 MALT lymphomas with t(14;18)(q32;q21), tumour cells showed strong homogeneous cytoplasmic expression of both MALT1 and BCL10. In 12/12 cases with evidence of t(1;14)(p22;q32) or variants, tumour cells expressed MALT1 weakly in the cytoplasm but BCL10 strongly in the nuclei. In all 67 MALT lymphomas with t(11;18)(q21;q21), tumour cells expressed weak cytoplasmic MALT1 and moderate nuclear BCL10. In MALT lymphomas without the above translocations, both MALT1 and BCL10, in general, were expressed weakly in the cytoplasm. Real-time quantitative RT-PCR showed a good correlation between MALT1 and BCL10 mRNA expression and underlining genetic changes, with t(14;18)(q32;q21)- and t(1;14)(p22;q32)-positive cases displaying the highest MALT1 and BCL10 mRNA expression respectively. These results show that MALT1 expression pattern is identical to that of BCL10 in normal lymphoid tissues but varies in MALT lymphomas, with high cytoplasmic expression of both MALT1 and BCL10 characterizing those with t(14;18)(q32;q21).     

Complex karyotypic anomalies in a bizarre leiomyoma of the uterus

Cytogenetic investigation of short-term cultures from a bizarre leiomyoma of the uterus, a tumor type not hitherto karyotypically characterized, revealed two abnormal clones with multiple complex rearrangements. Three-fourths of the aberrant cells were hypodiploid with the composite karyotype 38–44, XX,?6,?7,?10,?11,+20,?22, r(1), der(2) (:2p23→cen→2q13::1q21→1qter), der(2)t(2;9)(p21;q13), t(5;?)(q35;?), t(5;?),(q35;?), + der(5)t(5;15)(q11;q15), der(8)t(8;11)(q24;q13), t(15;?)(p12;?), der(16)t(12;16)(q13;p13),+r,+mar. The remaining abnormal mitoses were hypotetraploid, with chromosome numbers ranging from 74 to 86. These massively rearranged cells showed the same markers that were found in the hypodiploid clone, but in duplicate, indicating that this clone had arisen through polyploidization of hypodiploid cells. Flow cytometry revealed a DNA index of 1.03.     

Amplification of C-MYC as the origin of the homogeneous staining region in ovarian carcinoma detected by micro-FISH.

Homogeneous staining region (hsr), a cytogenetic indicator of gene amplification, has been frequently found in ovarian carcinoma (ovc). To identify the origin of the hsr, chromosome microdissection combined with polymerase chain reaction and fluorescence in situ hybridization (FISH) was applied to two human ovarian cancer cell lines, GR and MLS/P. The hsr probes were labeled with biotin or digoxigenin and hybridized to normal metaphase spreads to elucidate the chromosomal origin and regional localization of the amplified genes. FISH to normal metaphase spreads with the probe generated from the whole hsr-bearing chromosome from GR hybridized to 8q24, 2p13-->2q11.2, 10pter-->10p15, 10p12-->10q11.2, 5q23-->5q31, and 5q33-->5qter. For MLS/P, the hsr-bearing marker chromosome hybridized to 8q and 15q. In both cases, detailed FISH analysis revealed enhanced signal intensity at the 8q24 locus, which coincides with the chromosomal location of the C-MYC oncogene. To verify the involvement of C-MYC in hsr formation, in situ hybridization with a probe specific for the C-MYC oncogene was conducted and confirmed the amplification of C-MYC as the origin of the hsr. The whole hsr-bearing chromosome for GR is designated as rev ish der(10) (10pter-->10p15::8q24hsr:: 10p12-->10q11.2::8q24::2q11.2-->2p13::2p13 -->2q11.2::8q24::10q11-->10p11.2:: 5q23-->5q31::5q33-->5qter (wcp10+,D10Z1++,wcp2+,D2Z++,wcp5+,wcp8+ ,C-MYC++/hsr). The hsr-bearing marker for MLS/P is designated as rev ish der(8)(qter-->8q24::8q24::8q24-->8q10:: 8q10-->8q24::8q24::8q24-->8qter:: 15q11-->15qter)(wcp8+, D8Z1+,wcp15+,C-MYC++. FISH with the probe generated from the hsr of GR also painted the hsr in MLS/P, indicating that the two hsrs have shared homology, which indicates that the amplification of 8q24/C-MYC as the origin of hsr may be a nonrandom genomic alteration in ovc.     

Cytogenetic studies of primary cultures of esophageal squamous cell carcinoma

Cytogenetic analysis was performed on primary cultures of 21 squamous cell carcinomas of the esophagus (SCCE). Seven cases exhibited mosaic clonal chromosome abnormalities distributed as follows: two contained tetraploid cell populations, one with t(3;7)(p21;q11); two showed loss of the Y chromosome, one with double minutes; single cases demonstrated der(11)t(4;11)(q?27;q23); add(1)(p35) and del(4)(p12); and del(7)(p13), del(7)(q22q34), and der(11)t(7;11)(p?15;p?13). The remaining 14 cases had apparently normal karyotypes, possibly derived from stromal elements. These results demonstrate numerical abnormalities and the multiple occurrence of rearrangements involving chromosomes 7 and 11 in SCCE.     

Nonrandom chromosome changes in Kaposi sarcoma: cytogenetic and FISH results in a new cell line (KS-IMM) and literature review

The karyotype of a new tumorigenic Kaposi sarcoma (KS)-derived cell line, as defined by cytogenetic and fluorescence in situ hybridization (FISH) analysis is 49,XY,i(1)(q10),i(7)(p10),+i(7) (q10),+der(8)t(8;13)(p11;q11),-13,+del(14)(q22),+der(17)t(1;17)(p13;p13). Our aim was to point out some characteristics and recurrent chromosome changes probably playing a relevant role in the malignant progression of KS, by a comparison of the cytogenetic results obtained in the present study with data from the literature. The interpretation of the cytogenetic results is that KS development occurs by multiple steps: an initial reactive polyclonal cell proliferation is associated with chromosome instability; the cells in a later stage acquire clonal chromosome changes. If many chromosome changes are present, particularly 8q and 1q trisomy, 3p14-->pter deletion, 1p13, 13p14.3, 7q22, 8p11, 13q11, and 19q13 band rearrangements, KS acquires a neoplastic aggressive state.     

Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas

Cytogenetic investigation of short-term cultures from two leiomyosarcomas revealed complex karyotypic changes in both cases. The first tumor, a subcutaneous leiomyosarcoma of the knee, had the karyotype 70-80,XY, +X, +Y, +1, +1, +2, +2, +3, +3, +4, +4, +7, +7, +8, +8, +9, +10, +15, +15, +16, +16, +18, +19, +20, +21, +21, +22, +22,t(?;5)(5;21)(?;q35p11;q11), t(?;5)(5;21)(?;q35p11;q11), +del(11)(q22),der(13)t(12;13)(q13;q22),der(14)t(9;14)(p11;p11), +14p+, +t(20;?)(q13;?), +t(20;?)(q13;?), +2 mar. A polyploidized clone with 120-150 chromosomes was also observed. DNA flow cytometry revealed only one abnormal peak, corresponding to a DNA index of 1.76. The other tumor, a uterine leiomyosarcoma, had the karyotype 61-67, X, -X, +1, +3, +5, +6, +7, +8, +9, +12, +13, +15, +t(1;1)(p32;q32), +der(1)t(1;8)(p13;q11), +del(2)(p11), +del(2)(q22), +del(2)(q22), +del(3)(p13), +i(5p),t(8;14)(q24;q24), +der(8)t(8;14) (q24;q24), +del(10)(p12),der(11)t(11;15)(p15;q11),t(16;?)(p13;?),t(16;?)(q24;?), der dic(17) (17pter----cen----17q25::hsr::17q25----cen----17pte r), +t(19;?)(p13;?), +der dic(20)(20pter----cen----20q12::hsr::20q12----cen----+ ++20pter), +mar. The DNA index was 1.59. The finding in these leiomyosarcomas of rearrangements of the same regions of chromosomes 12 and 14 that are involved in the tumor-specific t(12;14)(q14-15;q23-24) of uterine leiomyoma indicates that the same genes in 12q and 14q might be important in the pathogenesis of benign and malignant smooth muscle tumors.     

MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells.

Among the genetic abnormalities reported to occur in mucosa-associated lymphoid tissue (MALT) lymphomas, the three translocations t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21) are of particular interest because they appear to be specific for, or at least closely related to this type of B-cell non-Hodgkin's lymphoma. These translocations affect the MALT1 (18q21) and BCL10 (1p22) genes. We retrieved 77 consecutive biopsies of MALT lymphomas (documented with frozen material) over a 10-year period and investigated these cases for the presence of these three translocations with fluorescence in situ hybridisation, along with the immunohistochemical analysis of the intracellular localisation of the BCL10 protein. The above-listed translocations occurred mutually exclusive and were detected in 10, 1 and 3% of the cases, respectively (the latter incidence being much lower than in the previously reported studies by one single group). These genetic rearrangements corresponded well with the aberrant subcellular localisation of the BCL10 protein as found by immunohistochemistry: t(11;18)(q21;q21) and (1;14)(p22;q32) were marked by a, respectively, moderate to strong nuclear BCL10 staining pattern while t(14;18)(q32;q21)-positive MALT lymphomas were characterised by a perinuclear BCL10 staining pattern. This study further supports the close interaction between the MALT1 and BCL10 proteins in the pathogenesis of MALT lymphomas and may indicate that BCL10 immunohistochemistry is a simple technique to identify those MALT lymphoma cases with an underlying genetic aberration.