B lineage acute lymphoblastic leukemia transformation in a child with juvenile myelomonocytic leukemia, type 1 neurofibromatosis and monosomy of chromosome 7 - Possible implications in the leukemogenesis

This report describes the case of an 8-month-old infant with a diagnosis of juvenile myelomonocytic leukemia (JMML) and type I neurofibromatosis that presented progression to B lineage acute lymphoid leukemia (ALL). The same rearrangement of gene T-cell receptor gamma (TCRgamma) was detected upon diagnosis of JMML and ALL, suggesting that both neoplasias may have evolved from the same clone. Our results support the theory that JMML may derive from pluripotential cells and that the occurrence of monosomy of chromosome 7 within a clone of cells having an aberrant neurofibromatosis type 1 (NFI) gene may be the cause of JMML and acute leukemia. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

X monosomy and balanced Robertsonian translocation in a girl with Turner Syndrome

We describe a case of X monosomy associated with a maternally inherited t(13;14) Robertsonian translocation in a girl with Turner syndrome. The girl's X chromosome was demonstrated to be maternally inherited, ruling out the hypothesis that the translocation exerted an interchromosomal effect on the origin of the monosomy. Chromosomes 13 and 14 showed biparental inheritance.

Monosomy 22 and del(10)(p12) in an ameloblastoma previously diagnosed as an adenoid cystic carcinoma of the salivary gland

Short-term cultures of a collagenase disaggregated ameloblastoma previously diagnosed as an adenoid cystic carcinoma of the salivary gland were shown by cytogenetic analysis to have the clonal karyotype 45,XY,del(10)(p12), -22. The data may indicate that the loss of genes of chromosome 22, as well as of 10p, could be a critical event in the evolutionary pattern of odontogenic neoplasias. (C) Elsevier B.V., 1996

Clonal monosomy of chromosome 21 in a case of myelodysplastic syndrome

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients

Purpose: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidentiologic variables.Experimental Design: Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis.Results: Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer.Conclusions: the significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.

Classical and molecular cytogenetic analysis in head and neck squamous cell carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Detection of numerical chromosome anomalies in interphase cells of benign and malignant thyroid lesions using fluorescence in situ hybridization

Benign and malignant thyroid tumors constitute a wide range of neoplasias showing recurrent chromosome abnormalities. In an attempt to characterize specific numerical chromosome abnormalities in thyroid tissues, We present here the findings from a study of archival samples depicted by 10 malignant tumors, 30 benign lesions, and 10 normal thyroid tissues. Fluorescence in situ hybridization was performed on noncultured samples using biotinylated centromere-specific probes for chromosomes 7, 10, and 17. Trisomy or tetrasomy 7 were present in 19 benign and in 7 malignant tumors. Trisomy 10 or 17 were observed in 18 adenomas or goiters and in 9 carcinomas, and monosomy 17 was seen in 2 carcinomas. Our findings suggest that such abnormalities are an in vivo phenomenon and may be important in the neoplastic proliferation of thyroid gland. (C) Elsevier B.V., 2000. All rights reserved.

GENETIC INSTABILITY IN NERVE SHEATH CELL TUMORS

After in vitro culture, we analyzed cytogenetically four acoustic nerve neurinomas, one intraspinal neurinoma and one neurofibroma obtained from unrelated patients. Monosomy of chromosomes 22 and 16 was an abnormality common to all cases, followed in frequency by loss of chromosomes 18 (three cases) and chromosomes 8, 17 and 19 (two cases). Trisomy of chromosome 20 was also detected in two cases. Structural rearrangements were detected at low frequencies, with del(10)(p12) being present in two cases. In addition, we observed cell subpopulations showing a certain degree of genetic instability, reflected by the presence of polyploid cells with inconsistent abnormalities, endoreduplications and telomeric associations resulting in dicentric chromosomes. It is probable that these cytogenetic abnormalities represent some kind of evolutionary advantage for the in vitro progression of nerve sheath tumors.

Cytogenetic alterations in chagasic achalasia compared to esophageal carcinoma

Patients with chagasic achalasia (megaesophagus) are liable to have an additional 1.7-20% possibility of developing esophageal squamous cell carcinoma (ESCC). We applied a fluorescence in situ hybridization technique in 20 such patients and found aneuploidies of chromosomes 7, 11, and 17 in 60% (12 of 20 specimens) and deletion of the TP53 gene in 54.5% (6 of 11 specimens; it was only possible to obtain data by FISH technique from 11 of the 20 achalasia patients). The main aneuploidies detected were chromosome 7 monosomy or trisomy (35%) in mid-third megaesophagus cases, and chromosome 17 monosomy or trisomy (25%) in distal-third cases. TP53 gene deletion was more frequent in mid-third (62.5%) than in distal-third megaesophagus cases (40%). In chagasic megaesophagus, no amplification of the cyclin D1 gene (CCND1) was observed. Comparing chagasic megaesophagus to ESCC, we found a higher frequency of aneuploidies in all 10 tumors. The main alterations were trisomy or tetrasomy of chromosomes 17 (90%), 11 (70%), and 7 (70%). Amplification of CCND1 was evidenced as a cluster in 70% of the tumors (22-99% of nuclei), while TP53 gene deletion occurred in 100%. To our knowledge, this is the first cytogenetic analysis of chagasic megaesophagus to show that aneuploidies of chromosomes 7, 11, and 17, and TP53 gene deletion might be related to increased risk for malignancy. (C) 2004 Elsevier B.V. All rights reserved.

Estudo citogenético em equinos para detecção de portadores de monossomia do cromossomo X

A cytogenetic study of 22 mares with fertility has showed that four of them had 63,X/64,XX mosaicism. The X-chromosome has presented the expected interstitial heterochromatic C - banding located in the long arm, besides of the usual centromeric band. The great variation of clinic signs observed in mares with mosaicism, could be due to the type of zygote or the time the mosaicism occured.

Interstitial long-arm deletion of chromosome 7 and ectrodactyly

An interstitial deletion of 7q21 was found in a boy with mental retardation, microcephaly, convergent strabismus, micrognathia, genital anomalies, and other findings, including ectrodactyly.

Multiple cytogenetic clones in a basal cell carcinoma

Chromosome analysis of short-term culture of a basal cell carcinoma showed five clonal chromosome abnormalities, t(9;14)(q12 or q13;p11), del(1)(q23 or q25), trisomy 5, trisomy 7, and monosomy X. In addition, several nonclonal structural and numerical changes were seen in the tumor cells.

Genetic alterations in benign lesions: Chronic gastritis and gastric ulcer

Aim: To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TP53 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. Methods: Gastric biopsies from normal mucosa (NM, n = 10), chronic gastritis (CG, n = 38), atrophic gastritis (CAG, n = 13) and gastric ulcer (GU, n = 21) were studied using fluorescence in situ hybridization (FISH) and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect H pylori. An association of the gastric pathologies and aneuploidies with H pylori infection was assessed. Results: Aneuploidies were increasingly found from CG (21%) to CAG (31%) and to GU (62%), involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG (P = 0.0143) and GU (P = 0.0498). No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% (5/11) and 12% (2/17) of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. Conclusion: The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with H pylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa. © 2006 The WJG Press. All rights reserved.

Investigação citogenética na síndrome mielodisplásica infantil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise citogenética e molecular do gene FOXO3 em síndrome mielodisplásica

Pós-graduação em Genética - IBILCE