R. Casalone

Cytogenetic analysis reveals clonal proliferation of smooth muscle cells in atherosclerotic plaques

SummaryCytogenetic analysis of primary cell cultures from human atherosclerotic fibrous plaques revealed clonal chromosome abnormalities in 13 of the 18 cases studied. Loss of the Y chromosome and del(13)(q14) were present as single clonal abnormalities in eight cases; in five cases separate clones were found involving loss of the Y and a XXY karyotype, trisomy 10 and 18, loss of the Y and trisomy 7. A variety of single numerical and structural abnormalities were present in all but two of the 18 cases. Immunocytochemical studies were performed on cells from the same cultures used for cytogenetic analysis using monoclonal antibodies to human leucocyte common antigen, to human vimentin and to muscle actin. The immunoreactivity was positive for actin in 70–80% of the cells; 100% of the cells were positive for vimentin and all cells were ALC negative. These results indicated that the chromosomal abnormalities are present in the smooth muscle cells of the plaque. The hypothesis is proposed that the proliferation leading to the atherosclerotic lesion may primarily represent a hyperplastic response to mechanical and biological injuries and that this reactive proliferation is, in turn, associated with a tendency to chromosome instability.

Correlation Between Cytogenetic and Histopathological Findings in 65 Human Meningiomas

The correlations between cytogenetic and histopathological findings were analyzed in 65 cases of human meningiomas. Clonal chromosome abnormalities were present in 28 cases (43%). The overall female/male ratio was 1.7, but it was 1.1 in the group of 28 cases with chromosomal abnormalities. Abnormalities of chromosome 22 as sole abnormality predominate in the female patients. The mean age of patients with normal karyotype was significantly lower (50.7 years) than that of patients with chromosome changes (57.3 years). The tumor origin was predominantly at the base in the patients with normal karyotype but different at the convexity, falx cerebri, and spinal cord. The five abnormal cases from the spinal cord all showed involvement of chromosome 22. The proportion of chromosome anomalies was different in the various histological types, and a significant difference was found between the meningotheliomatous (23%) and psammomatous (58%) types. The cytogenetically abnormal cases of the psammomatous type all showed involvement of chromosome 22. In three patients with multiple meningiomas, we found different karyotypes in the different tumors of the same patient, which may indicate a multifocal origin of the tumors.

Pathogenetic significance of "pure" monosomy 7 in myeloproliferative disorders. analysis of 14 cases

SummaryMonosomy 7 is frequent in acute myeloid leukaemia (AML) and in preleukaemic dysmyelopoietic syndromes but often it is not the only chromosome anomaly associated with these conditions. We report 14 patients with “pure” monosomy 7 and their clinical and haematological data are analysed in order to clarify the possible implications of this chromosome anomaly. The following points are considered:1)In spite of the apparent variability of clinical forms in which monosomy 7 is found, several characteristics are common to all monosomy 7 patients, i.e. the presence of a preleukaemic phase and blood and marrow features suggesting the early involvement in the disease of all marrow cell lines. The different diagnoses associated with monosomy 7 are correlated with different steps of a unique myeloproliferative disease whose typical course can be reconstructed.2)Monosomy 7 has a negative prognostic value. When it is found in a preleukaemic disorder it indicates a high risk of progression to AML, while in AML it implies recurrent infections poor response to therapy and short survival.3)The significance of the lack of Colton blood group antigens in monosomy 7 patients is discussed, with particular regard to the fact that the patients in whom this lack was found are the only ones who had not received transfusions in the months before the tests were done.4)The finding of defective neutrophil chemotaxis in monosomy 7 patients is confirmed and the clinical importance of this fact is emphasized.5)The data on the 14 patients support the opinion that AML, in general, is heterogeneous in origin. It is postulated that monosomy 7 is a marker of a specific pathogenetic pathway of AML, which implies the beginning of the malignancy in a pluripotent stem cell.

Large T antigen coding sequences of two DNA tumor viruses, BK and SV40, and nonrandom chromosome changes in two glioblastoma cell lines

The T antigen (TAg) coding sequences of two DNA tumor viruses, BKV and SV40, were detected by Polymerase Chain Reaction (PCR) amplification followed by Southern-blot hybridization in two human glioblastoma multiforme derived cell lines. RT-PCR analysis indicated that these two TAg coding sequences were expressed in both tumor cell lines carrying the viral early region DNAs. Moreover, analytical polyacrylamide gel electrophoresis (PAGE) and DNA sequence analyses showed that the amplified PCR products are indistinguishable from the TAg coding sequences of BKV and SV40 wildtype strains. Cytogenetic study performed in the two cell lines showed unbalanced changes, mainly gains of chromosomes 3p, 5, 6, 7, and 19 and losses of chromosomes 3, 3q, 16, 9p22-->pter, 18, and 20. Excess of chromosomes 6 and 7 are common to the two cell lines. The putative role of the TAg of the two DNA tumor viruses in transformation and karyotype changes is discussed.

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.

Cerebral germ cell tumor and XXY karyotype

Metaphases from a cultured cerebral germ cell tumor (CGCT) in a boy with a 46,XY constitutional karyotype had 47 chromosomes with an additional X chromosome and a translocation (1;21)(q11;p11). CGCT appear to be nonrandomly associated with Klinefelter syndrome, and a supernumerary X chromosome and trisomy of the 1q21-->1qter region may be clonal abnormalities in these tumors. The predisposition of Klinefelter patients to develop CGCT may be due to the pathogenetic relevance of the extra X chromosome both as an acquired and a constitutional abnormality.

Rearrangement of three chromosomes (Nos. 2,8, and 21) in acute myeloblastic leukemia. Evidence for more than one specific event☆

Abstract A complex rearrangement involving chromosomes No. 2, 8, and 21 with four break points was found in a case of acute myeloblastic leukemia (AML) of the M 2 type. The clinical implications are briefly discussed and an attempt is made to define the role of chromosomal events leading to translocation (8;21) in AML.

Patial trisomy 1 due to 1/17 translocation in Ph'-Positive chronic myelocytic leukemia

SummaryA patient with chronic myelocytic leukaemia (CML) had the Philadelphia chromosome from the standard 9/22 translocation, a partial trisomy 1 secondary to an unbalanced 1/17 translocation, and a more recent clone with the addition of trisomy 22. This is the third case of partial trisomy 1 associated with the Philadelphia chromosome. Trisomy 1 in haematological disorders is discussed with reference to its clinical significance in CML, the segment of chromosome no. 1 involved, and the mechanisms of origin of the partial trisomies. Anomalies of chromosome 1, although not specific to any of them, seem to be important in the development of myeloproliferative disorders and of neoplasms in general.

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.

Cytogenetic and interphase cytogenetic analyses reveal chromosome instability but no clonal trisomy 8 in dupuytren contracture

The results of cytogenetic and FISH analysis performed in 26 cases of Dupuytren contracture are reported. Clonal or sporadic chromosome changes were found in 18 cases (69%). Clonal changes consisted of: +2, +16, -10, -Y, add(1)(p23), del(2)(q21), t(3;16)(p21;q24), add (3)(p24), del(18)(q21), t(Y;14)(p12;q24), +mar. The results differ from those obtained in normal palmar fascia used as control, in which -Y and +Y were the only clonal changes found in 2 of 11 analyzed cases (18%). No clonal trisomy 8 was found. FISH analysis performed in 11 cases (centromeric probe specific for chromosome 8) failed to show the presence of a cell population with +8. Clonal and sporadic structural changes were different from case to case and no clustering breakpoint was observed. The significance of the chromosome instability leading to clonal and sporadic chromosome changes not specific to Dupuytren contracture are discussed.