Typical NF2 and LTZR1 mutations are retained in an immortalized human schwann cell model of schwannomatosis.

Human SCs play a primary role in SWN, a rare genetic disorder in which patients develop multiple schwannomas. So that, their isolation and immortalization could represent an irreplaceable tool to investigate the disease etiopathology. Although few clones of tumoural SCs have been obtained, unfortunately they present genetic, morphological and biological characteristics that do not fully represent the original cells.

Cyclic AMP induces reversible EPAC1 condensates that regulate histone transcription.

The second messenger cyclic AMP regulates many nuclear processes including transcription, pre-mRNA splicing and mitosis. While most functions are attributed to protein kinase A, accumulating evidence suggests that not all nuclear cyclic AMP-dependent effects are mediated by this kinase, implying that other effectors may be involved. Here we explore the nuclear roles of Exchange Protein Activated by cyclic AMP 1.

Blue marine therapy: Sea as a trove of natural anticancer drugs.

The great variability of marine habitats and the species that live there allows the development of organisms with unique characteristics. These represent an excellent source of natural compounds and are therefore interesting in the search for new bioactive molecules. In recent years, many marine-based drugs have been commercialized or are currently under investigation, mainly in the treatment of cancer.

Analysis and pharmacological modulation of senescence in human epithelial stem cells.

Human epithelial stem cells (ESCs) are characterized by long-term regenerative properties, much dependent on the tissue of origin and varying during their lifespan. We analysed such variables in cultures of ESCs isolated from the skin, conjunctiva, limbus and oral mucosa of healthy donors and patients affected by ectrodactyly-ectodermal dysplasia-clefting syndrome, a rare genetic disorder caused by mutations in the p63 gene. We cultured cells until exhaustion in the presence or in the absence of DAPT (γ-secretase inhibitor; N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine T-butyl ester).

The displacement of frataxin from the mitochondrial cristae correlates with abnormal respiratory supercomplexes formation and bioenergetic defects in cells of Friedreich ataxia patients.

Friedreich ataxia (FRDA) is a neurodegenerative disease resulting from a severe decrease of frataxin (FXN). Most patients carry a GAA repeat expansion in both alleles of the FXN gene, whereas a small fraction of them are compound heterozygous for the expansion and a point mutation in the other allele. FXN is involved in the mitochondrial biogenesis of the FeS-clusters.

Acute promyelocytic leukemia with a cryptic insertion of RARA into PML on chromosome 15 due to uniparental isodisomy: A case report.

Acute promyelocytic leukemia is a myeloid disorder that is characterized by the specific t(15;17) variant in ~98% of cases. The typical hypergranular and microgranular or hypogranular types exist, and are frequently associated with disseminated intravascular coagulopathy. Rare cases of promyelocytic leukemia-retinoic acid receptor α (PML-RARA) fusion without the reciprocal RARA-PML have been reported in cytogenetically normal samples.

45,X product of conception after preimplantation genetic diagnosis and euploid embryo transfer: evidence of a spontaneous conception confirmed by DNA fingerprinting.

Background: Preimplantation genetic screening (PGS) provides an opportunity to eliminate a potential implantation failure due to aneuploidy in infertile couples. Some studies clearly show that twins following single embryo transfer (SET) can be the result of a concurrent natural conception and an incidence as high as 1 in 5 twins has been reported. In our case PGS was performed on trophectoderm (TE) biopsies by quantitative polymerase chain reaction (qPCR).

Lung cancer in which the hypothesis of multi-step progression is confirmed by array-CGH results: A case report.

The pathogenesis of lung cancer has not been fully elucidated and biological markers acting as predictors of tumor evolution and aggressiveness remain unidentified. The multi-step hypothesis, suggesting a progression from adenomatous hyperplasia (AAH) to adenocarcinoma (AC) through bronchioalveolar carcinoma (BAC), was highlighted in a previous cytogenetic study performed in a single case. The present study reports the results of an array-comparative genomic hybridization (a-CGH) analysis performed on the DNA obtained from the previously reported case that presented AAH, BAC and AC in one lung.

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy.

Background: The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy.

Cytogenetic findings in lung cancer that illuminate its biological history from adenomatous hyperplasia to bronchioalveolar carcinoma to adenocarcinoma: A case report.

The biological and chronological evolution of lung cancer remain to be fully elucidated. A multi-step carcinogenesis hypothesis suggests a progression from atypical adenomatous hyperplasia (AAH) through bronchioalveolar carcinoma (BAC) to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated. We report a case of a patient diagnosed by computed tomography (CT) with lung cancer in the superior right lobe who also presented with a pure ground-glass opacity (GGO) in the inferior lobe, while the middle lobe appeared normal.

Fluorescent in situ hybridization (FISH) in the differential diagnosis of ground-glass opacities in the lung.

Computed tomographic (CT) screening for lung cancer has increased the detection rate of nodules manifesting as ground-glass opacities (GGOs). The natural history of this new entity it is not well known nor is the factors that influence the growth, progression and malignant potential. This genetic study was performed in order to identify molecular markers with possible diagnostic and prognostic significance to differentiate lesions with malignant or benign profiles.

A fluorescence in situ hybridization (FISH) procedure to assist in differentiating benign from malignant melanocytic lesions.

Objective: Misdiagnosis of melanocytic lesions can result in unnecessary psychological distress to patients, under- or overtreatment, inaccurate prognosis and improper follow-up and family member surveillance. It is well recognized that, despite many attempts to 1) put forth a set of histologic criteria that can accurately and reproducibly be used to diagnose melanocytic lesions, and 2) identify reliable markers of malignancy as an adjunct to routine histopathology, misdiagnoses still occur in a significant number of cases.

Method: A multi-color FISH probe mixture has been devised to assist pathologists in differential diagnosis of difficult melanocytic lesions.

Chromosomal abnormalities in miscarriages after different assisted reproduction procedures.

About 10-15% of all recognised pregnancies end in spontaneous abortion and around 60% of these show a chromosomal abnormality. The finding of an abnormal karyotype allows one to avoid unnecessary and controversial testing and treatment, providing accurate reproductive and genetic counselling to the couple. Consequently, chromosome study of products of conception (POC) is routinely performed in our Institute, starting from 2002.

Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer.

To explore the clinical significance of the level of HER2/neu gene amplification in a homogenous cohort of 33 patients with HER2-positive metastatic breast cancer (MBC) and available tumor samples treated with a trastuzumab-based regimen, we retrospectively performed dual-color fluorescence in-situ hybridization test and correlated them for each patient with time-to-progression (TTP) and overall survival (OS). We obtained values of HER2/chromosome 17 centromere (CEP17) ratio ranging from 2.5 to 21 (median 7.

Administration of temozolomide during and after radiotherapy for newly diagnosed high-grade gliomas excluding glioblastoma multiforme.

Primary brain high-grade gliomas, excluding glioblastoma are rare and heterogeneous tumors, showing different characteristic mutations and a better prognosis than glioblastomas. The addition of chemotherapy to the radiotherapy in the newly diagnosed disease has not been established yet. We treated 9 patients with newly diagnosed tumors with temozolomide at 75 mg/m2 for 7 days a week during standard radiotherapy, followed by six cycles at 200 mg/m2 on days 1-5 every 28 days.

Clinical and molecular cytogenetic studies in three infertile patients with mosaic rearranged Y chromosomes.

Isodicentrics (idic) are structural anomalies of the Y chromosome associated with a 45,X cell line and a broad spectrum of phenotypes. We characterized the rearranged Y chromosomes from three azoospermic males by fluorescence in-situ hybridization (FISH) and PCR. Chromosome study was performed on lymphocytes and testicular biopsy.

Prenatal diagnosis of del(9)(p24): a sex reverse case.

Background: We report on a fetus with sex reversal and del(9)(p24) consequent to a malsegregation of a maternal balanced complex translocation involving chromosomes 7, 9 and 11.

Methods: Fluorescence in situ hybridization (FISH) was performed in order to verify the presence of the SRY gene and the absence of DMRT1 and DMRT2 genes located in 9p24.3 region and frequently associated with sex reversal.

Unusual cytogenetic findings in a synovial sarcoma arising in the paranasal sinuses.

A fresh specimen from an intracranial tumor, which was histopatologically classified as a synovial sarcoma, was investigated cytogenetically. The direct method failed to give any information due to a lack of mitotic cells after treatment with 70% acetic acid, whereas 6-day cultures showed a 45,XY,del(6q),-10 karyotype. The histologic evaluation was consistent with a synovial sarcoma, which is well characterized from a cytogenetic perspective and involves a t(X;18)(p11;q11) in more than 95% of cases.

FISH characterization of two supernumerary r(1) associated with distinct clinical phenotypes.

Only a few reports on supernumerary r(1) chromosomes associated with a clinical phenotype have been published. We describe two unrelated patients with congenital malformations and developmental delay who were found to have a de novo supernumerary r(1) in 50% (Case 1) and 80% (Case 2) of the examined cells. Conventional cytogenetic techniques (QFQ, CBG, and DA-DAPI), complemented by fluorescence in situ hybridization studies using alpha satellite probes, showed that both small marker chromosomes (SMCs) primarily consisted of the centromere and heterochromatin of chromosome 1, a conclusion that was also supported by chromosome 1 painting.

Reduced growth hormone (GH) responsiveness to combined GH-releasing hormone and pyridostigmine administration in the Prader-Willi syndrome.

Objective: It is unclear whether the blunted GH secretion in Prader-Willi Syndrome (PWS) is a true deficiency, or merely secondary to obesity. We have investigated the role of obesity in the blunted GH secretion in PWS.

Design: We studied the GH response to a combined administration of GHRH (1 microgram/kg i.