Comparative cytogenetics in different populations of the cavernicolous diplopod Pseudonannolene strinatii (Diplopoda, Pseudonannolenidae)

Different populations of Pseudonannolene strinatii Mauriès, 1974 collected from three caves in Iporanga, state of São Paulo, were cytogenetically compared using techniques of conventional coloration, C-banding and silver nitrate impregnation. Specimens were morphologically similar and small cytogenetic differences were observed between the populations with relation to the distribution of constitutive heterochromatin.

Cytogenetic characterisation of childhood acute lymphoblastic leukemia in Nicaragua

BACKGROUND: Within the frame of a twinning programme with Nicaragua, The La Mascota project, we evaluated in our study the contribution of cytogenetic characterization of acute lymphoblastic leukemia (ALL) as prognostic factor compared to clinical, morphological, and immunohistochemical parameters. METHODS: All patients with ALL treated at the only cancer pediatric hospital in Nicaragua during 2006 were studied prospectively. Diagnostic immunophenotyping was performed locally and bone marrow or blood samples were sent to the cytogenetic laboratory of Zurich for fluorescence in situ hybridization (FISH) analysis and G-banding. RESULTS: Sixty-six patients with ALL were evaluated. Their mean age at diagnosis was 7.3 years, 31.8% were >or=10 years. Thirty-four patients (51.5%) presented with hyperleucocytosis >or=50 x 10(9)/L, 45 (68.2%) had hepatosplenomegaly. Immunophenotypically 63/66 patients (95%) had a B-precursor, 2 (3%) a T- and 1 (1.5%) a B-mature ALL. FISH analysis demonstrated a TEL/AML1 fusion in 9/66 (14%), BCR/ABL fusion in 1 (1.5%), MLL rearrangement in 2 (3.1%), iAMP21 in 2 (3.1%), MYC rearrangement in 1 (1.5%), and high-hyperdiploidy in 16 (24%). All patients but two with TEL/AML1 fusion and high-hyperdiploidy were clinically and hematologically in the standard risk group whereas those with poor cytogenetic factors had clinical high-risk features and were treated intensively. CONCLUSIONS: Compared to Europe, the ALL population in Nicaragua is older, has a higher proportion of poor prognostic clinical and hematological features and receives more intensive treatment, while patients with TEL/AML1 translocations and high-hyperdiploidy are clinically in the standard risk group. Cytogenetics did not contribute as an additional prognostic factor in this setting.

Cytogenetic characterization of childhood acute lymphoblastic leukemia in Nicaragua.

BACKGROUND: Within the frame of a twinning programme with Nicaragua, The La Mascota project, we evaluated in our study the contribution of cytogenetic characterization of acute lymphoblastic leukemia (ALL) as prognostic factor compared to clinical, morphological, and immunohistochemical parameters. METHODS: All patients with ALL treated at the only cancer pediatric hospital in Nicaragua during 2006 were studied prospectively. Diagnostic immunophenotyping was performed locally and bone marrow or blood samples were sent to the cytogenetic laboratory of Zurich for fluorescence in situ hybridization (FISH) analysis and G-banding. RESULTS: Sixty-six patients with ALL were evaluated. Their mean age at diagnosis was 7.3 years, 31.8% were >or=10 years. Thirty-four patients (51.5%) presented with hyperleucocytosis >or=50 x 10(9)/L, 45 (68.2%) had hepatosplenomegaly. Immunophenotypically 63/66 patients (95%) had a B-precursor, 2 (3%) a T- and 1 (1.5%) a B-mature ALL. FISH analysis demonstrated a TEL/AML1 fusion in 9/66 (14%), BCR/ABL fusion in 1 (1.5%), MLL rearrangement in 2 (3.1%), iAMP21 in 2 (3.1%), MYC rearrangement in 1 (1.5%), and high-hyperdiploidy in 16 (24%). All patients but two with TEL/AML1 fusion and high-hyperdiploidy were clinically and hematologically in the standard risk group whereas those with poor cytogenetic factors had clinical high-risk features and were treated intensively. CONCLUSIONS: Compared to Europe, the ALL population in Nicaragua is older, has a higher proportion of poor prognostic clinical and hematological features and receives more intensive treatment, while patients with TEL/AML1 translocations and high-hyperdiploidy are clinically in the standard risk group. Cytogenetics did not contribute as an additional prognostic factor in this setting.

The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial.

The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses-in a three-step manner-using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

Estudio preliminar del retardo mental en la población de Rovira (Tolima, Colombia)

El retardo mental se caracteriza por limitaciones en el desempeño como resultado de significativas deficiencias de la inteligencia y la conducta adaptativa. En Colombia, la mayor parte de los pacientes con esta alteración no reciben evaluación genética. El objetivo de este trabajo es evaluar y caracterizar el retardo mental en un grupo de personas con esta condición en la población de Rovira (Tolima, Colombia) e identificar los posibles factores asociados. La metodología consistió en realizar un diagnóstico clínico preliminar de 25 pacientes con retardo mental y realizar la correspondiente toma de muestras de sangre y orina para efectuar los exámenes correspondientes. Se realizaron estudios bioquímicos (cloruro férrico, nitrosonaftol, nitroprusiato de sodio, Benedict, cromatografía para la detección de aminoácidos y carbohidratos) y citogenéticos (bandeo G). Para la detección de plaguicidas, se realizó un muestreo aleatorio en diferentes puntos de todo el recorrido del sistema de distribución de agua y ciertos lugares del centro del municipio de Rovira. Con este fin, se recolectaron 20 muestras de agua y 20 muestras de tomate, elegidas al azar, de los diferentes sitios de distribución y cultivos de la hortaliza. Se identificó una familia de tres hijos afectados (dos mujeres y un hombre) con retardo mental, lo cual sugiere un componente genético en este caso. Las pruebas metabólicas fueron negativas y los cariotipos normales. Se plantea la necesidad de realizar pruebas moleculares que incluyan el síndrome de X-frágil para complementar el estudio y realizar consejería genética. En cuanto a los resultados y el análisis pertinente de las muestras para organofosforados, el 100% de éstas resultaron positivas. Se reportó un 60% de positividad en las muestras de agua y del 100% en las muestras de tomate, para el caso de los carbamatos; sin embargo, para el caso de los organoclorados, el 100% de las muestras estudiadas resultaron negativas.

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

Genomic imbalances associated with mullerian aplasia

Background: Aplasia of the mullerian ducts leads to absence of the uterine corpus, uterine cervix, and upper (superior) vagina. Patients with mullerian aplasia (MA) often exhibit additional clinical features such as renal, vertebral and cardiac defects. A number of different syndromes have been associated with MA, and in most cases its aetiology remains poorly understood. Objective and methods: 14 syndromic patients with MA and 46, XX G-banded karyotype were screened for DNA copy number changes by similar to 1 Mb whole genome bacterial artificial chromosome (BAC) array based comparative genomic hybridisation (CGH). The detected alterations were validated by an independent method and further mapped by high resolution oligo-arrays. Results: Submicroscopic genomic imbalances affecting the 1q21.1, 17q12, 22q11.21, and Xq21.31 chromosome regions were detected in four probands. Presence of the alterations in the normal mother of one patient suggests incomplete penetrance and/or variable expressivity. Conclusion: 4 of the 14 patients (29%) were found to have cryptic genomic alterations. The imbalances on 22q11.21 support recent findings by us and others that alterations in this chromosome region may result in impairment of mullerian duct development. The remaining imbalances indicate involvement of previously unknown chromosome regions in MA, and point specifically to LHX1 and KLHL4 as candidate genes.

Contribuição à citogenética de testudines e análise de assimetria flutuante em Eretmochelys imbricata, Cheloniidae

This work has contributed to knowledge of the order Testudines from cytogenetic and morphological point of view. With regard to the aspects proposed cytogenetic characterization of the species Mesoclemmys tuberculata (n = 5), endemic to the Caatinga biomes, through conventional techniques of cytogenetics and molecular levels. This species presented 2n = 58, NF = 64, the first submetacentric pair, the second metacentric and third subtelocentric, and the other microchromosome telocentric. This species showed a nucleolar bearing pair, coincident with the 18S ribosomal rDNA and that proved to be heterochromatic. Small heterochromatic blocks were also found in the centromeres of the largest chromosomes, as well as terminal regions in most other chromosomes of the complement, that were GC +. Telomeric sequences showed variable patterns of signal intensity, with some repeats more intense in microchromosomes and subtly in the larger ones. When compared with other species of the genus, the G-banding patterns showed a marked similarity between them. The first karyotypic description of the species will aid in future studies and the understanding of evolutionary aspects of this family. From the morphological point of view, we carried out studies of fluctuating asymmetry in sea turtle Eretmochelys imbricata, using methods of benchmarking between hatchlings and adults and their implications for natural selection. Data were collected at two different times: first during the spawning female and the second during the outbreak and birth of the nest. The analyzed characteristics consisted of measurements of length and width of front and rear flippers (CANT, LANT, CPOS and LPOS) also collected data on the number of hull plates, side plates (NPL), the surrounding plates (NPCIRC), and plastron; plates power plants (NPP), inframarginais plates (NPIM). With the values of asymmetry we calculated the value of strict heritability for these traits, the calculation was based on only one parent. A nonparametric analysis Mann-Whitneywas performed to compare the groups (females X hatchlings, newborn hatchlings X dead hatchlings). Adult females showed no bilateral fluctuating asymmetry (FA = 0) on the number plates of the hull and plastron, while offspring, living and dead, showed a greater level of variation in these meristic parameters. In the analysis of females x hatchlings we found a significant difference between the levels of asymmetry in hoof plates (p=0.006) an the width of hindlimbs (p=0.001). Levels of FA suggest an accurate indicator as to the viability or maintenance of the individual to the reproductive phase. The coefficient of heritability (h2) of FA , obtained from the regression analysis, showed that both have low and not statistically significant values(p> 0.1). In the case of exclusion of the effective role of genetics in the generation of FA, reproductive strategies based on high number of subsidiaries products, such as those observed in E. imbricata seems to implicate the production of individuals with high level of developmental instability

New recurrent deletions in the PPAR gamma and TP53 genes are associated with childhood myelodysplastic syndrome

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

DNA gains at 8q23.2: a potential early marker in head and neck carcinomas

Gains or amplifications involving chromosome arm 8q are one of the most recurrent chromosomal alterations in head and neck tumors. To characterize previously reported gains, we performed fluorescence in situ hybridization (FISH) using the sequences BAC RP1179E1 and 8-centromere PMJ 128 as probes. Gains and/or amplifications were detected in all 19 cases evaluated by FISH. The FISH analysis, but not G-banding, revealed homogeneously staining region in three cases. We conclude that gains of one or more genes on chromosome arm 8q may be important for the early stages of head and neck carcinomas. (C) 2003 Elsevier B.V. All rights reserved.

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

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

Cytogenetic characterization of Brycon amazonicus (Spix et Agassiz, 1829) (Teleostei: Characidae) from Caicara del Orinoco, Venezuela

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Translocation (11;19)(q23;p13.3) associated with a novel t(5;16) (ql3;q22) in a patient with acute myelocytic leukemia

A novel association of t(11;19)(q23;p13) and t(5;16)(q13;q22) was detected by G-banding and spectral karyotyping studies in an 18-year-old patient. While balanced t(11; 19) has been often described in acute myelocytic leukemia (AML) French-American-British Cooperative Group subtypes M4 and M5, this patient was diagnosed with the variant AML-M4 with eosinophilia (AML-M4Eo), which is associated with abnormalities in 16q22 and has good prognosis. However, the patient relapsed after allogeneic transplant and died within 2 years of diagnosis, which suggests that the association of these two translocations correlates with a poor prognosis. This report expands the molecular basis of the variability in clinical outcomes and adds the novel t(5;16)(q13;q22) to the spectrum of chromosome 16q22 abnormalities in AML. (C) 2003 Elsevier B.V. All rights reserved.

Comparative cytogenetics in different populations of the cavernicolous diplopod Pseudonannolene strinatii (Diplopoda, Pseudonannolenidae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CYTOGENETIC REPORT OF A MALE BREAST-CANCER

The cytogenetic findings on G-banding in an infiltrating ductal breast carcinoma in a 69-year-old man are reported. The main abnormalities observed were trisomy of chromosomes 8 and 9 and structural rearrangement in the long arm of chromosome 17 (add(17)(q25)). Our results confirm the trisomy of chromosome 8 in the characterization of the subtype of ductal breast carcinomas and demonstrate that chromosome 17, which is frequently involved in female breast cancers, is also responsible for the development or progression of primary breast cancers in males.