Citogenetica molecolare in oncoematologia

Cancer may be regarded as genetic disease because of presence of gene mutation and/or anomalies as consequence of exposure to mutagens, carcinogens, errors of DNA replication or damaged DNA repair. Actually WHO indicates the cytogenetic analysis as essential in the initial evaluation of haematological neoplasms. Repeated analyses are suggested for monitoring the desease evolution and the response to therapy. FISH may be usefull to detect cryptic anomalies not detected by routine techniques. Our aim was to introduce FISH analyses both at the diagnosis and in the reassessment of cases previously misdiagnosed, then we performed standard analyses in QFQ banding, at the beginning and at different stages of the disease, as well as FISH experiments with various probes: single locus, subtelomeric, whole chromosome painting, chromosome enumeration probes/alphoid sequencies and BAC/PAC probes. In the last three years 1055 samples have been analyzed by standard techniques and 433 by FISH. Consultation of database of 2367 cases by the year 2000 until now highlighted a noteworthy increase in requests of all cytogenetics analyses, mainly for lymphoid pathologies thirteen time higher in the last year. Our experience suggest that evolution from single anomaly to complex kariotypes is followed by disease progression, which may be controlled by different therapies, so a constant cytogenetic monitoring is required, using both standard and molecular cytogenetic methods

Unbalanced rearrangement der(9;18)(p10;q10) and JAK2 V617F mutation in a patient with AML following post-polycythemic myelofibrosis

Polycythemia Vera (PV) is a clonal myeloproliferative disorder characterized by excessive erythrocyte production, which may evolve into myelofibrosis and acute myeloid leukemia. Transformation to myelofibrosis occurs in 15-20% of cases and leukemic transformation in 5-10% of patients. The median survival time is 8-11 years and the median age at diagnosis is over 60 years. Normal karyotype is present at diagnosis in the majority of patients, while during transformation several acquired chromosome anomalies are present as trisomy 9 and gains in 9p

Effects of Cadmium chloride on human fetal cells in vitro

The principal aim of this work was to demonstrate the feasibility of tests with substances known as teratogenic in vivo on cell types which are the real target of their teratogenic effects. To this purpose Cadmium chloride has been tested on human amniotic fluid cells using the Chromosome aberrations (CA) and Sister chromatid exchanges (SCE) tests

Morphological findings in malformed fetuses with normal karyotype

In our Department morphological findings on fetuses from therapeutic interruption of pregnancy or spontaneous abortion are performed since ten years in order to correlate the ultrasound and/or chromosomic diagnosis with a real presence of malformations. The fetopathologic examination generally agrees with the chromosomal diagnosis, while in several cases it is possible to find malformations also in presence of a normal karyotype (Gitz, 2011). In our experience over the past 5 years we have found that 17 fetuses with a normal karyotype showed different heterogeneous ultrasound malformations. Only in 2 cases the fetuses died in uterus (17th and 22nd weeks of gestation), the other cases, aged between 14th and 23rd weeks of gestation, went from voluntary abortions. In 7 cases the karyotype was defined by amniocentesis while in the remaining 10 was determined by fetal fibroblasts culture; in only 30% of the observed cases the couple had carried out a genetic evaluation. External malformations were present in 16 fetuses, often related to the face (such as micrognathia, low-set of ears, flattened nasal bridge, cleft lip) or limb (short, curved, stubby) of spine (spina bifida) or genitalia (hypospadias). Malformations of internal organs were present in 10 cases, often affecting the cardiovascular system (complex heart defects and abnormal origin of the greath vessels), and nervous system (meningocele, agenesia of the corpus callosum, ventricular dilatation and Arnold-Chiari malformation); less frequent were malformations of other systems (digestive, respiratory and urinary). There was a single case of situs viscerum inversus associated with complex cardiac malformations and atresia of the bucco-pharyngeal membrane. These results indicate that the fetal morphological study is useful not only to confirm but often to supplement and complete the ultrasound data. Moreover genetic evaluation, utilizing fetopatholgical study, may have an important role in defining the diagnostic and clinical procedure, especially in relapses with malformed fetus and normal karyotype

Bacterial community acquired pneumonia in HIV-infected inpatients in the highly active antiretroviral therapy era

Introduction: Highly active antiretroviral therapy (HAART) has deeply modified HIV/AIDS related morbidity and mortality. However, bacterial community acquired pneumonia (BCAP) still represents one of the most frequent causes of morbidity in HIV-infected patients with an inpatient 10% mortality rate. Objectives: We retrospectively studied the characteristics of BCAP in consecutive HIV-infected inpatients hospitalized from 1999 to 2004 and evaluated the presence of risk factors and the influence of combination antiretroviral therapy receipt on BCAP outcomes. Results: We studied 84 BCAP episodes in 76 HIV-infected inpatients (63 males and 13 females) aged 27–80 years. Thirty-two (42.1%) patients were receiving combination antiretroviral treatment (CART) while 44 (57.9%) were not treated (NART). BCAP incidence progressively increased from 1999 to 2004. The overall percentage of injection drug users was > 84%, of smokers > 88% and alcohol abusers > 32% with no statistical difference between CART and NART. Streptococcus pneumoniae was the most frequently identified pathogen (60%). Time to clinical stability was significantly longer in NART in respect of CART (p = 0.011). In multivariate analysis, CDC stage C, CD4 cell count < 100 × 106 cells/l, and S. pneumoniae etiology were predictors for time to clinical stability > 7 days, while receipt of antiretroviral therapy was protective. The percentage of deaths did not differ between CART and NART; most patients had a CD4 count < 200 × 106 cells/l or severe concomitant diseases. Conclusions: The incidence of BCAP was high in HIV-infected inpatients observed in the present study mainly due to HIV infection itself, IVDU, alcohol abuse and smoking habit. A longer time to clinical stability was associated with advanced HIV infection and with S. pneumoniae etiology, while receipt of antiretroviral therapy was protective. Injection drug abuse treatment, alcohol abuse and smoking cessation programs, antiretroviral treatment adherence support and pneumococcal vaccination should be implemented to reduce the incidence and to improve the outcomes of BCAP in HIV-infected patients

Pure partial trisomy of 6p12.1-22.1 secondary to a familial 12/6 insertion in two malformed babies

We describe two malformed infants with trisomy 6p12.1âp22.1 due to 12/6 interchromosomal insertion. The phenotypic data observed in these patients are compared chiefly with a case cytogenetically similar described by Villa et al. [A. Villa, E.G. Gomez, L. Rodriguez, R.H. Rastrollo, M.E. Martinez Tallo, M.L. Martinez-Frias, Interstitial tandem duplication of 6p: a case with partial trisomy (6)(p12p21.3), Am. J. Med. Genet. 90 (2000) 369â375]. All three infants are trisomic for a genomic segment which largely overlaps that reported as duplicated in previous cases, but with the addition of a more proximal segment, extending from 6p12 to 6p21. We suggest that some of their phenotypic anomalies are due to the trisomy of this chromosomal region. We also speculate on the possible role played by the TFAP2B (Transcription Factor AP2-beta) gene, which is one of the genes mapped on the duplicated segment

Partial trisomy of the long arm of chromosome 1: prenatal diagnosis, clinical evaluation and cytogenetic findings: case report and review of the literature

Partial trisomy of the long arm of chromosome 1 is a relatively rare cytogenetic anomaly. Its phenotype has still not been completely defined, because of the cytogenetic heterogeneity of the cases so far described. We report a prenatal case of partial 1q trisomy associated with partial monosomy 4q, secondary to balanced maternal translocation t(1;4). The trisomic segment extended from 1q31.1 to qter and the monosomy 4q was from 4q35.2 to qter. The phenotypic anomalies found by post-mortem and autopsy examinations were compared with those of similar cases reported in the literature. We performed standard cytogenetics and fluorescence in situ hybridization. Cerebral ventriculomegaly, present in our case, seemed to be a constant feature in partial 1q trisomies, so this cerebral malformation could be considered as the main echographic marker for this chromosomal imbalance and trisomy 1q should be added to the list of chromosomal abnormalities associated with ventriculomegaly

Patau syndrome with long survival in a case of unusual mosaic trisomy 13

A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on different tissues, including skin fibroblasts from differently pigmented areas, are also reported