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 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.     

Significance of chromosomal abnormalities in a malignant giant cell tumor of bone.

Cytogenetic analysis of a malignant giant cell tumor of the sacrum from a 62-year-old female revealed the following chromosomal complement: 47,XX, -1, -11, +22,del(2)(p22),t(7;7) (p22;q32), +der(1)t(1;11;21)(p32;q13;q22), +der(19)t(19;?)(q13.4;?), der(8)t(8;?)(p11;?), der(7)t(17;?)(p13;?). Metaphase cells with 92-127 chromosomes sharing identical structural abnormalities detected in the near-diploid cells were also observed. Several of these abnormalities have previously been described in the benign giant cell tumors supporting a direct relationship between these benign and malignant neoplastic counterparts.     

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.     

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.     

Chromosome analyses in chronic lymphocytic leukemia and related B-cell neoplasms

Chromosome analyses were performed by routine G-banding in 29 patients with B-cell chronic lymphocytic leukemia (B-CLL), six with immunocytoma (IC), three with centroblastic-centrocytic (cb-cc) lymphoma, and one with hairy cell leukemia (HCL). Ages of the patients were between 46 and 81 years (mean, 63 years). 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was used as a mitogen to stimulate leukemic B-cells in 72-hour cultures. Twenty-one patients had one or more chromosomal abnormalities; and in 13 patients, they were clonal; 18 patients had a normal karyotype. Seven patients had trisomy 12 (three B-CLL, two IC, two cb-cc lymphoma); two (B-CLL) had it as the sole abnormality. One patient with B-CLL had trisomy 18 as the sole abnormality, and one with IC had trisomy 18 in combination with trisomy 19. One patient with B-CLL had t(1;6)(p36;p21) as a clonal structural abnormality. A t(11;14)(q13;q32) was consistently observed in one patient with cb-cc lymphoma together with inv(1) (p22p36), der(4)t(4;?)(p16;?), del(6)(q13) and other variable changes. One patient with morphologically atypical B-CLL had t(1;11)(p36;q13) together with der(X)t(X;?)(q26;?), der(3)t(3;?)(q29;?), der(8)t(4;8)(q12;q24.1) and additional variable changes. Both patients with these complex karyotypes were in an advanced stage of disease (Binet stage C) and died within 3-6 months after chromosome analysis.     

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.     

Clonal structural chromosome aberrations in fibrous dysplasia

Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22), add(12)(p13)/46,idem,t(3;8)(p21;q13),add(10)(q26),der(15)del(15)(q15q22)ins(15;?)(q15;?)/46,idem,-X, + 2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations.     

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.     

Karyotypic analysis of two related cervical carcinoma cell lines that contain human papillomavirus type 18 DNA and express divergent differentiation

The cell lines C-4I and C-4II were established in culture from a nonkeratinizing squamous carcinoma of the uterine cervix. Both lines contain human papillomavirus (HPV) type 18 DNA (Brandt et al., Cold Spring Harbor Laboratories, 5:179, 1987) and both are hypodiploid with similar, but not identical, karyotypes. Each line expresses multiple characteristics of ectocervical epithelial differentiation, but the characteristics differ between the lines. In the present study, G banding of the lines showed that cells of both lines have two normal chromosomes 1-5, 8-10, 13, 16, and 17, one normal chromosome 12 and 14, and no normal chromosomes 15 and 18. The lines share three abnormal chromosomes, der(8)t(8q;12q), der(18)t(18q;?), and i(5p). There are specific differences between the lines. C-4I has two normal chromosomes 6, while C-4II has one; C-4II has two chromosomes 11 and der(18)t(18q;?), while C-4I lacks both chromosomes 11 and has one der(18)t(18q;?). Each line has unique markers that include del(11)(p11), del(22)(q12), and del(21)(q21) in C-4I and i(15q), der(X)t(Xq;9p), der(6)t(6p;14q), and del(4)(q21) in C-4II. The results show that these phenotypically distinct lines are derived from the same clone and that the 8q arm (the site of HPV 18 integration) is present in three copies in both lines. They also define several chromosome rearrangements that are compatible with the expression of specific differentiation markers.     

Chromosome abnormalities in a pancreatic adenocarcinoma

Short-term cultures initiated from a pancreatic adenocarcinoma were cytogenetically investigated. The composite karyotype was 74-76,XX,+X,+2,+3,+del(3)(p21),+5,+5,+der(7) t(1;7)(q21;p22),+der(7),del(8)(p21),+del(8)(p21),+der(8)t(8;?)(q24; +),+9,+9,+10,+10,+11,+11,+12,+13,+14,+der(14)t(14; +)(p11;?),+der(16)t(15;16)(q11;p13),+der(16),+der(17)t(17;?) (p11;?),+der(17),+18,+20,+20,-21,-21,+22,+22,+1-3mar. A comparison with the few previously cytogenetically characterized cases of this tumor type reveals no consistent abnormalities.     

Cytogenetic findings in a case of pediatric glioblastoma.

We report a patient with glioblastoma multiforme (GBM) which showed stable and unstable telomeric associations involving the short arms of chromosomes 4 and 7. The karyotype was hyperdiploid, with chromosome numbers ranging from 84 to 87 in all cells, and showed a single stemline with variations in the number of marker chromosomes, teleomeric associations, and double minutes (dmin). The karyotype designation is 83-86,XX,-X,rea(X),-4,tas(4;7)(p16;?p22),der(6)t(6;?)(p21;?), -8, -9, der(9)t(9;?)(?p11;?), dup(9)(p12p23), -10 x 2, del(10)(p11), -11,del(11)(p11), -12, der(12)t(12;?) (p13;?),-13, -14 x 2,der(14)t(14;?) (p11;?), -16 x 2, -19, -21 x 2, -22 x 2, + 9-13mar, + dmin. Loss of the short arm of chromosome 10, structural aberrations of the short arm of chromosome 9, and dmin are consistent findings in GBM, whereas the high chromosome number is less common. Chromosome instability associated with the phenomenon of telomeric association/fusion has not been reported in GBM.     

Challenge in diagnosis of CD56+ lymphoproliferative disorders: two cases of CD56+CD33+ lymphoma/leukemia

Two cases of CD56+CD33+ leukemia/lymphoma are reported. The patient in case 1 presented with skin rash, diffuse lymphadenopathy, and hepatosplenomegaly. Blasts with monocytoid and lymphoid features were present in the peripheral blood. The tumor cells expressed HLA-DR, CD4, CD33, CD38, and CD56. Cytogenetic analysis revealed del(2)(p13),del(9)(q22),add(6)(q25),add(12)(p12),-13,-18, and -20. The clinicopathologic features were similar to those of blastic natural killer cell leukemia/lymphoma or type 2 dentritic cell leukemia. The patient in case 2 presented with generalized weakness and skin erythema not responding to antibiotics. Circulating blasts with monocytoid features were seen in the peripheral blood. The tumor cells expressed CD7, CD13, CD33, CD38, and CD56, and cytogenetic analysis revealed -5,add(7)(p22),-8, del(10)(p11.2),-12,der(13; 14)(p10;p10),+14,-16,-18,-19, and del(20)(q13.1). The clinicopathologic features were consistent with a myeloid/ natural killer cell precursor acute leukemia. Both disorders are aggressive hematopoietic malignancies that have similar clinical presentation and morphology but differ in immunophenotype and cytogenetic features.     

Atypical cytogenetic aberrations in two childhood peripheral primitive neuroectodermal Tumors

Atypical cytogenetic abnormalities were detected in peripheral primitive neuroectodermal tumors (PPNET) of the extremity in two children. One had an osseous tumor with a balanced reciprocal translocation, t(5;9)(q22;q32), and had a complete response to therapy. The other had a non-osseous tumor with an interstitial deletion, del(18)(q12.2q21.2), was resistant to combination therapy, and at autopsy had evidence of possible clonal evolution with the karyotype 46,XX der(8)t (8;8)(p11.2;q13), inv(16)(p13.2q12), del(18)(q12.2q21.2). Neither tumor demonstrated the t(11;22)(q24;q12) typically found in Ewing's sarcoma and PPNET, suggesting heterogeneity of the cytogenetic aberrations seen in this rare childhood malignancy.     

Recessive cancer genes in meningiomas? An analysis of 31 cases

Cytogenetic studies on 31 human meningiomas revealed clonal abnormalities in 14 of them. Monosomy 22 was present in three cases as the only abnormality, and in five it was associated with monosomy 18, monosomy 14, loss of X, loss of Y, and trisomy 20, respectively. We found a number of rearrangements involving chromosome #22: an i psu dic(22)(pter----q11::q11----pter) in two cases and a t(18;22)(q12;q11) in another case. Two cases showed a complex translocation involving #7 and #14: t(2;7;14)(q23;q36;q22) and t(1;7;14)(q25;q32;q22), respectively. Other clonal chromosome abnormalities were del(1p) (present in two cases); der(9)t(9;?)(q34;?); der(7)t(7;?)(q31;?); der(22)t(22;?)(q11;?); and a 9p+ chromosome. The relevance for the pathogenesis of human meningiomas of these chromosome anomalies is also discussed with reference to the previous literature. The possible involvement of recessive cancer genes present on the long arm of chromosome #22 is also discussed.     

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.     

Clonal chromosome abnormalities in two liposarcomas

Two liposarcomas were analyzed with chromosome banding technique. The sole chromosomal abnormality in one of the tumors, a mixed type (myxoid and round cell) liposarcoma, was t(12;16)(q13;p11), a rearrangement previously reported to be associated with myxoid liposarcoma. The other tumor, a pleomorphic liposarcoma, displayed massive numerical rearrangements (modal chromosome number 94-112), and numerous, mostly unidentifiable, marker chromosomes. The following clonal structural aberrations were recognized: del(1)(p22), del(1)(q23), t(7;?)(p22;?), i(17q), and t(19;?)(q13;?).     

Chromosome analysis of 97 primary breast carcinomas: Identification of eight karyotypic subgroups

Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1;16)(q10;p10), del(1)(q11–12), del(3)(p12–13p14–21), and del(6)(q21–22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12–13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.     

Cytogenetic findings in a pleomorphic xanthoastrocytoma

We report a pleomorphic xanthoastrocytoma with an abnormal clonal cell line of 48,XY, +3, +5, -20, -22, +der(7)t(7;?)(p22;?), +der(20)t(15;20)(q11;q13).     

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.