R. Righi

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.

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.

Cytogenetic and Interphase FISH Analyses of 73 Basal Cell and Three Squamous Cell Carcinomas: Different Findings in Direct Preparations and Short-Term Cell Cultures

Cytogenetic analysis performed on 73 sporadic basal cell carcinomas (BCCs) and three squamous cell carcinomas (SCCs) showed different findings in direct preparations (24 hours) and in short-term cell cultures. Except for loss of the Y chromosome, not one of the other clonal (+6, +16, add(2)(q37), del(3)(q13), add(1)(p31), and near triploidy) or sporadic changes found in direct preparations was found in cell cultures and vice versa. Clonal trisomy 6 found in two BCC direct preparations and demonstrated by interphase fluorescence in situ hybridization in 8 other cases seems to be a nonrandom change in basal cell carcinoma. Immunohistochemistry showed that the cell type investigated was different in the two methods of analysis used: epithelial in direct preparations and fibroblastic in cell cultures. Thus, the results obtained in direct preparations indicate the BCC or SCC epithelial karyotype, whereas the aberrations found in cell cultures indicate the presence of chromosome instability in the fibroblastic stroma. The apparent lack of correspondence between direct and indirect preparations and the presence of clonal chromosome changes in both epithelial and stromal cells suggest tumor cell heterogeneity of BCC. The fibroblastic stroma seems to be implicated in the neoplastic process. This is not evident in SCC, in which clonal changes are present only in direct preparations. The chromosomal distribution of the breakpoints involved in structural changes in direct and cell culture preparations is random; together with those reported in the literature, the breakpoints found in BCC cultures show, however, a cluster to 1p36, 3q13, 9q22, 14p11, 15p11, and Xp11 bands. We did not find any significant correlations between BCC cytogenetic results and the clinical data (site, age, sex, recurrence). The incidence of cases of BCC (38%) and of SCC (100%) showing clonal chromosome changes agree with their benign and malignant nature, respectively. Finally, a significantly high incidence of constitutional inv(9) and dup(9)(q11q21) was found in the group of patients with BCC.

Molecular cytogenetics, RFLP analysis and clinical characterization of a de novo trisomy 10p case

A new case of a de novo trisomy 10cen-->10pter is described. The karyotype was exactly defined by high resolution banding and FISH analysis; the chromosome aberration was of maternal meiotic origin as demonstrated by RFLP analysis. Clinical data are reported and correlated with other trisomy 10p cases from the literature. A critical review of the literature was made to define the phenotype of trisomy 10p syndrome.

Chromosome changes in benign prostatic hyperplasia and their significance in the origin of prostatic carcinoma

Cytogenetic studies of benign prostatic hyperplasia (BHP) are scarce. We analyzed primary cell cultures obtained from biopsies of prostatic tissues from 10 patients (mean age: 60.7 years) with histologic diagnosis of BHP to compare the eventual chromosome changes with those reported in prostatic adenocarcinoma. Clonal chromosome abnormalities were noted in five of the 10 cases, with loss of Y chromosome in all. In one case, a clonal t(1;20) was observed with a -Y clone. Different numerical and structural sporadic abnormalities were evident in eight. Chromosome 1 was the chromosome most frequently involved in sporadic rearrangements. We concluded that -Y is a frequent nonrandom chromosome abnormality in BHP in this sample of patients. Immunohistochemical studies showed that loss of Y occurs in fibroblasts and not in epithelial cells; therefore, this anomaly is not related to cancer development.

Clonal chromosome changes in renal carcinoma do not correlate with clinical stages and histopathologic grades

We analyzed the correlations between chromosome abnormalities and clinical and histopathologic characteristics in 77 cases of renal cell carcinoma (RCC). Chromosome changes such as +5,+7,+8,+10,+18,+X,+Y, and -Y have been excluded from the analysis because they also occur in nonneoplastic kidney tissue and cytogenetic analysis indicates that these anomalies are not involved in tumor progression. The most frequent specific chromosome abnormalities in this sample were 3p rearrangements, trisomy 17, and hyperdiploidy and were not related to tumor stage or grade or to development of distant metastases.

Clonal chromosome changes in non-neoplastic ureters

Cytogenetic analysis was performed on 23 samples from non-neoplastic ureters. Clonal chromosome abnormalities were found in eight. They were: loss of Y chromosome, as a single abnormality (five cases) or associated with trisomy 10 and 20 (one case) or with trisomy 2 (one case); and duplication of Y chromosome (one case). Different numerical and structural sporadic abnormalities were found in nine cases. Immunohistochemical analysis and direct observation using the inverted microscope showed that the cells were mainly of the fibroblastic type. FISH analysis with chromosome 7 alpha-satellite probes failed to detect the presence of trisomy 7 in three epithelial cases tested.

A new acute myeloid leukemia case with STAT5B-RARA gene fusion due to 17q21.2 interstitial deletion

Chiara Pessina , Claudia Basilico , Angelo Genoni, Emanuela Meroni, Lorenzo Elli, Paola Granata, Rossana Righi, Francesco Pallotti, Barbara Mora, Andrea Ferrario, Francesco Passamonti and Rosario Casalone SMeL Citogenetica e Genetica Medica, ASST Sette Laghi, Varese, Italy; Dipartimento di Medicina Specialistica, Ematologia, ASST Sette Laghi, Varese, Italy; Dipartimento di Scienze Chirurgiche e Morfologiche, Universit a degli Studi dell’Insubria, Varese, Italy; Dipartimento di Medicina Clinica e Sperimentale, Ematologia, Universit a degli Studi dell’Insubria, Varese, Italy

Acute myeloid leukemia with associated translocation t(15;17) and 11q23/MLL abnormality.

The classification of acute myeloid leukemia (AML) recognizes a subgroup of diseases with recurring genetic abnormalities. Translocation (15;17) is the marker of acute promyelocitic leukemia (APL) and is associated with good prognosis [1]. 11q23/MLL abnormality has been detected in about 4% of AML [2], but never in APL [3]. 11q23/MLL abnormality is related to a previous treatment with topoisomerase inhibitors and also to a monocytic differentiation of blasts [4]. AML with 11q23/MLL has an adverse prognosis, comparable to AML with unfavourable karyotype. In this letter, we describe a case of AML with t(15;17) and t(11;22)(q23;q11.2) abnormalities; as far as we know, this association has not been reported in literature. A 64-year-old woman was admitted to our department because of cytopenia. The patient had no history of myelodysplasia, radiotherapy or chemotherapy, or toxic drug exposure. Clinical examination was negative. Blood cells count showed anaemia (haemoglobin 8.4 g/dL), leucopenia (0.876 10 cells/L) and thrombocytopenia (226 10 cells/L). Myeloid blast cells (8%) were found in peripheral blood smear. Bone marrow examination showed a blastic myeloid infiltration. Blast cells were 35% of nucleated cells and were hypogranular and myeloperossidase positive without similarities to promyelocytic blasts. No Auer’s rod was observed. Blast cells immunophenotype showed strong positivity for CD33, CD13, CD34, CD38 and a moderate expression of CD15 and CD19. HLA-DR, CD10, CD7, CD56 were negative. No morphologic evidence of dyserythropoiesis was detected by bone marrow biopsy. There were no signs of disseminated intravascular coagulation or accelerated fibrinolysis. Cytogenetic analysis revealed the association of t(15;17)(q22;q21) and t(11;22)(q23;q11.2) (WCP 11 and WCP 22 Vysis) abnormalities in all the metaphases analyzed (Figure 1). Reverse transcription polymerase chain reaction (RT-PCR) subsequently confirmed the presence of PML/RARa Bcr1 transcript and fluorescence in situ hybridisation (FISH-painting) confirmed the presence of t(11;22)(q23;q11.2) (Figure 2). Interphase FISH analysis with Vysis LSI MLI Dual Color probe, Break Apart Rearrangement probe showed that MLL gene region (11q23) was involved in the rearrangement (Figure 3). Karyotype and FISHpainting analysis for t(11;22) on lymphocytes were negative, therefore excluding an inherited chromosome translocation. The patient received induction therapy with alltrans-retinoic acid (ATRA) and idarubicin and