Chromosome rearrangements in two uterine sarcomas

Cytogenetic analysis of short-term cultures from two uterine sarcomas revealed clonal chromosome abnormalities in both cases. A locally recurrent mixed mesodermal tumor had the karyotype 61,XX,+2,+3,+del(5)(q11),+6,+7,+del(7)(q32),+8,+8,+8,+10, -11,-11,+der(11)t(1;11)(q12;p15),+der(11)t(1;11)(q12;p15),+der(11)t(1;11)(q12;p15),+del(12)(q14q21),+13,+15,del(17)(q23),+20. The other tumor, a lung metastasis from a uterine leiomyosarcoma, had several karyotypically abnormal clones. Two of them consisted of highly aberrant cells with modal chromosome numbers of 82 and 153, respectively, but because of insufficient quality the complex anomalies could not be identified. Various chromosomal changes that included translocations, deletions, insertions, and numerical rearrangements (always with extra chromosome 7 material) were identified in pseudo- or near-diploid cells, resulting in nine additional cytogenetically abnormal clones.     

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.     

Cytogenetics of sacral chordoma.

Only four cases of chordoma have been described cytogenetically. We report the cytogenetic findings of a fifth case. Chromosome analysis of a primary sacral chordoma from a 69-year-old man showed the following chromosome complement: 43,XY,-2,-3,del(4)(q32),-6,+7,-11,der(12)t(9;12)(q12;p11),add(16)(q23),- 20,add(22)(q13),+mar.     

Multiple clonal chromosome aberrations in two thymomas

Cytogenetic investigations of two thymomas of different histopathology revealed unrelated clonal karyotypic changes: 44,XY,+X,inv(2)(p25q13),del(6)(q15),-8,-16,-17 in a cortical thymoma, and 48-49,XX,+del(X)(q24),+i(5p),+?del(7)(q22),der(11)t(1;11)(q23;q25),t(11; ?)(p15;?),-18,+r in a mixed-type thymoma. These are the first thymic tumors of epithelial origin that have been investigated with banding technique.     

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.     

Endometrial stromal sarcoma with clonal complex chromosome abnormalities. Report of a case and review of the literature.

Only eleven endometrial stromal sarcomas (ESS) with clonal chromosomal abnormalities have been reported in the literature. Of these, four have been reported to harbor the t(7;17) translocation. We report here an additional ESS that exhibited clonal complex chromosome abnormalities not described earlier: 38,XX,-1,del(1)(q11),-2,add(2)(p13),-3,der(4)add(4)(p12)psu dic(4;14)(q35;q11.2), add(6)(p21.3),add(7)(q22),del(7)(p11.2p13),-8,-9,add(9)(q34),- 10,add(10)(q24),-11,-11,ins(12;?) (q13;?),-14,-14,-15,ins(15;?)(q22;?),add(16)(q22),add(17)(q11.2),- 18,der(18)t(7;18)(q11.2;p11.2),-19, add(20)(p13),add(21)(p11.2),-22,add(22)(p11.2),+6mar in metaphase cells from primary short-term culture.     

Direct chromosome analysis of seven primary colorectal carcinomas.

Chromosome studies were performed on direct preparations of seven cases of primary colorectal carcinomas. Two cases had relatively simple chromosome changes: 48,XY,+8,+21/51, XY,+8,+9,+10,+i(17q),+21, and 47,der(X)t(X;14)(q11;q11)-Y,t(6;18)(p22;q24)+7,+8,der(19)t (19;?)(q13;?). The five others had complicated deletions and translocations; 1p- was noted in five cases, and i(17q) was noted in three cases.     

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.     

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.     

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.     

Atypical congenital mesoblastic nephroma. Report of a case with karyotypic and flow cytometric analysis

Atypical congenital mesoblastic nephroma is a rare infantile renal tumor that may behave aggressively in older infants. A case of atypical congenital mesoblastic nephroma occurring in an 8-month-old hispanic male was analyzed by routine histopathologic, cytogenetic, and retrospective flow cytometric analysis for DNA ploidy. Light microscopy revealed marked hypercellularity. The karyotype was abnormal, with the following configuration: 45,XY,-1,-3,-9,-9,-15,-17,-21,+del(1)(q21q25),+der(3), t(3;9;15)(q23;p22;q11),+der(9),t(3;9;15) (q23;p22;q11),+der(9),t(9;?) (p?22;?),+r21, + mar. Retrospective DNA ploidy analysis revealed a DNA index of 1.0. The significance of karyotypic changes occurring in mesenchymal renal tumors of this type is currently unknown. Cytogenetic analysis might be of prognostic value in these potentially aggressive tumors.     

Multiple cytogenetic abnormalities in a case of osteosarcoma

Cytogenetic analysis of a highly malignant osteosarcoma in a 17-year-old girl revealed extremely complex karyotypic changes with several different clonal numerical and structural chromosome aberrations. The composite karyotype was interpreted as 39–41,X,t(X;9)(q11;p24), −1,der(1),−4,−4,−5,i(7q),−8,del(8)(q21),t(10;19)(p13;q13),del(11)(p11p13),t(12;18)(q24;q12), −13,13q+,−14,14p+,−15,15q+,17p+,19q+,−21,+22,+3–6 mar.     

Multiple structural chromosome rearrangements, including del(7q) and del(10q), in an adenocarcinoma of the prostate

Cytogenetic analysis of a poorly differentiated adenocarcinoma of the prostate revealed the complex karyotype: 76-86,X, -Y, +X, +X, +del(X)(q24), +t(1;10) (p22;q24), -2, +der(2) t(1;2;?)(p32;q24p13;?), +der(2)t(1;2;?) (p32;dq24p13;?), +3, +3, +4, +5, +5, +6, +7, +del(7) (q22), -8, +der(8)t(8;?)(q24;?), + der(8)t(8;?)(q24;?), +9, +10, +10, +der(10)t (1;10)(q24;q22), +del (10)(q23), +11, +11, +12, +der(12)t(4;12)(q11;p11), +der(12)t(4;12) (q11;p11), +14, +der (15)t(1;15)(q21;p11), +t(16;?) (q21;?), +17, +18, +19, +19, +20, +20, +21, +22, +2-5 mar. The karyotype contains deletions of both 7q and 10q, abnormalities that also have been described previously in prostatic adenocarcinomas, and which hence may represent primary chromosomal rearrangements in this type of cancer.     

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.     

Common chromosome aberrations in the proximal type of epithelioid sarcoma

A new case of the proximal type of epithelioid sarcoma with a complex karyotype 70-98 <4N>,XX,-X,-X,+5,i(5)(q10),+7,del(7)(q31),i(8)(q10)x3 approximately 4,del(12)(p13),der(18)ins(18:?) (q11;?)del(18)(p11). ish der(18)ins(18;X)del(18)(p11)(wcp18+,wcpX+),+20,+20,dmin [cp9] is described. Both, dual-color FISH using probes specific for OATLI1/OATL2 genes and RT-PCR analysis excluded the presence of t(X;18), typical for synovial sarcoma. Our case together with the previously published ones suggest that the presence of i(8)(q10), losses of 12p and 18p together with the gain of chromosome 20 may represent a common cytogenetic aberrations in the proximal type of epithelioid sarcoma.     

Pediatric renal cell carcinoma: clinical, pathologic, and molecular abnormalities associated with the members of the mit transcription factor family

We describe the clinical features, outcome, pathology, cytogenetics, and molecular aspects of 13 pediatric papillary renal cell carcinomas during a 19-year period. Seven cases (54%) had translocations involving Xp11.2 (TFE3). They were identified by cytogenetic, molecular, and/or immunohistochemical analyses. All Xp11.2+ translocations were TFE3+ by immunostaining. Cytogenetic and/or polymerase chain reaction analyses identified 3 cases with t(X17) and 1 case with t(1;17), and all had additional translocations. Histologic features in common in TFE3+ tumors also were present in some TFE3- tumors. One TFE3- tumor had complex cytogenetic abnormalities, 55XY,+2,del(3)(p14),+7,+8,+12,+13,+16,+17,+20[11 ], and 2 cases had normal karyotypes. None had t(6;11)/TFEB+ immunostaining. Five cases had focal, weak MITF tumor immunostaining. The key clinical findings were as follows: (1) The presence of an Xp11.2 (TFE3) translocation frequently is associated with advanced stage at initial examination. (2) All patients who underwent complete, partial nephrectomy with clear margins (adequate only for stage 1) and resection of metastases were alive and relapse-free at last follow-up. (3) The mean +/- SD event-free survival and overall survival rates at 5 years were both 92% +/- 7.4%. (4) One patients with a TFE3+ and MITF+ tumor and 66-87,XXY,der(1)t(1;8)del(4)(q?) der(11)t(11;15)der17t(X;17 abnormalities died 9 months after diagnosis.     

Karyotypic findings in two cases of male breast cancer

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.     

Comparative cytogenetic analysis between cyclophosphamide-sensitive and -resistant lines of acute myeloid leukemia in the Lewis Brown Norway hybrid rat

An animal model of acute myeloid leukemia (AML) has been developed in the Brown Norway (BN) rat and has successfully been introduced into the Lewis x BN F₁ hybrid (LBN) and designated LBN AML. The original LBN AML is sensitive to the chemotherapeutic agent cyclophosphamide (CY). Recently, a CY-resistant cell line of LBN AML has been established. To characterize this animal model of human leukemia better, we analyzed and compared the chromosomal makeup of both the CY-sensitive and CY-resistant LBN AML lines. The CY-sensitive LBN AML cultures contained two cell lines—line 1 (88%):41, XX, –1, –2, –9,del(12)(q16),+der(1)t(1;?8)(p13;q31),+der(2)t(2;9)(p11;q11); and line 11 (12%): 41,XX,–1,–2,–9,del(12),del(20)(q13)+der(1)t(1;?8)(p13;q31),+der(2)t(2;9)(p11;q11). The recently developed CY-resistant AML cells contained two cell lines—line 1 (88%): 41,XX,–1,–2,–9,del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?),?t(8;?)(q24;?),del(12)(q16),+der (1)t(1;?8)(p13;q31),+der(2)t(2;9)(p11;q11); and line II (12%): 42,XX (probably represents host contamination). The new chromosomal aberrations in the CY-resistant line 1 [del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?), and ?t(8;?)(q24;?)] suggest a possible interrelationship between these secondary karyotypic abnormalities and acquisition of resistance to the chemotherapeutic agent.     

Evolution of a near-triploid karyotype in a secondary erythroleukemia

We report a case of erythroleukemia (EL;FAB M6), preceded by a myelodysplastic phase, in a 50-year-old male 8 years after treatment for Hodgkin's lymphoma. Cytogenetic analysis of bone marrow at time of diagnosis of EL revealed three cell lines: 1) 28 of 53 cells (53%) were hypodiploid, 43,XY,-5,-7,-12; 2) 23 of 53 cells (43%) were near-triploid, stemline 67-69,XY,+2,del(5)(q11.2),+del(5)(q11.2),+6,-7,+8,-9,-11,-12,+15,-16,der (17)t (17;?) (p11.2;?),-18,-20,-20,+22,+r, + mar (relative to a complete triploid cell); 3) 2 of 53 cells (4%) were normal 46,XY. The relative monosomies of 5, 7, and 12 in both abnormal lines suggest that the near-triploid line evolved from the hypodiploid line. A single hypodiploid cell with both del(5) and der(17) chromosomes that appeared identical to those in the near-triploid line suggests that polyploidization occurred after these structural rearrangements. While EL is not characterized by any well-defined structural abnormality, reported cases are frequently hypodiploid, with occasional cases of polyploidization, as in our patient, EL in adults without previous neoplasia or recognized mutagenic exposure has been shown to have loss or deletion of chromosomes 5 and 7, also characteristic of myelodysplastic syndromes and secondary leukemia. Our patient had a relative lack of chromosomes 5 and 7 in both abnormal clones, as well as a del(5)(q11) in the near-triploid line. This case of EL clearly demonstrates the evolution of a complex near-triploid line from a hypodiploid line, with chromosome abnormalities typical of both EL and secondary leukemia.     

Cytogenetic study of malignant triton tumor: a case report

Malignant triton tumor (MTT) is a highly malignant neoplasm, classified as a variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. Few cytogenetic studies of MTT have been reported using conventional cytogenetic analysis. Here, we report a comprehensive cytogenetic study of a case of MTT using G-banding, Spectral Karyotyping(), and fluorescence in situ hybridization (FISH) for specific regions. A complex hyperdiploid karyotype with multiple unbalanced translocations was observed: 48 approximately 55,XY,der(7)add(7)(p?)dup(7)[2],der(7) t(7;20)(p22;?)ins(20;19)[5],der(7)ins(8;7)(?;p22q36)t(3;8)t(8;20)[15],-8[5],-8[19],r(8)dup(8), +der(8)r(8;22)[4],-9[9],der(11)t(11;20)(p15;?)ins(20;19)[22],der(12)t(8;12)(q21;p13)[21],der(13) t(3;13)(q25;p11),-17,-19,der(19)t(17;19)(q11.2;q13.1),-20,-22,+4 approximately 7r[cp24]/46,XY[13]. The 1995 International System for Human Cytogenetic Nomenclature was followed where possible. Note that breakpoints were frequently omitted where only SKY information was known for a small part of an involved chromosome. Our analysis revealed some breakpoints in common with those previously reported in MTT, MPNST, and rhabdomyosarcoma, namely 7p22, 7q36, 11p15, 12p13, 13p11.2, 17q11.2, and 19q13.1. FISH showed high increase of copy number for MYC and loss of a single copy for TP53.