Parallel evaluation of cell‑based phage display panning strategies: Optimized selection and depletion steps result in AML blast‑binding consensus antibodies.

Phage display technology (PD) is a powerful technique for the generation of tumor‑targeting antibodies. However, there are a number of different selection methods established in different laboratories around the world. Cell‑based PD panning methods using primary tumor cells are particularly heterogeneous between laboratories, which can lead to inconsistent results.

[Mucoepidermoidcarcinoma - Importance in molecular pathology].

Mucoepidermoid carcinoma is the most common primary salivary gland malignancy and its tumor grading has an important prognostic significance. The 5 year overall survival rate is significantly higher for low grade mucoepidermoid carcinomas than for intermediate grade and high grade mucoepidermoid carcinomas. The translocation of t(11;19)(q21;p13) with the resulting CRTC1-MAML2 transfusion appears to be of prognostic relevance in patients with mucoepidermoid carcinoma.

A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells.

Primary cardiac angiosarcomas are rare tumors with unfavorable prognosis. Pathogenic driver mutations are largely unknown. We therefore analyzed a collection of cases for genomic aberrations using SNP arrays and targeted next-generation sequencing (tNGS) of oncogenes and tumor-suppressor genes.

Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.

Myelodysplastic syndromes (MDS) are hematopoietic disorders characterized by ineffective hematopoiesis and progression to acute leukemia. In patients ineligible for hematopoietic stem cell transplantation, azacitidine is the only treatment shown to prolong survival. However, with the availability of a growing compendium of cancer biomarkers and related drugs, analysis of relevant genetic alterations for individual MDS patients might become part of routine evaluation.

Patient with three euchromatic supernumerary marker chromosomes derived from chromosomes 1, 12, and 18: characterization and evaluation of the aberrations.

The genetic relevance of small supernumerary marker chromosomes (sSMCs) depends on their content of euchromatin. In case of mosaicism, the phenotype of the carrier furthermore is influenced by the distribution of the marker in the body. In the majority of reported cases no correlation of the degree of mosaicism in the tissue(s) analyzed and the phenotype could be detected.

Duplication 3q13.11q23: Longitudinal study in a patient over a period of more than 7 years and refinements of the breakpoints.

In 2006, we reported the first case with a pure duplication of proximal 3q. In these rare aberrations, detailed clinical and developmental investigations at different ages are required to provide sufficient phenotypic documentation. Clinical and psychological differences were therefore regularly documented in our case.

Rare interstitial deletion 9q31.2 to q33.1 de novo: longitudinal study in a patient over a period of more than 20 years.

The female carrier of a de novo interstitial deletion 9q [karyotype 46,XX,del(9)(q31.2q33.1)] was followed up over a period of more than 20 years.

First report of a partial trisomy 3q12-q23 de novo--FISH breakpoint determination and phenotypic characterization.

We present a 1-year-old boy with mild mental retardation, postnatal growth retardation, and facial dysmorphisms such as frontal bossing, laterally accentuated bushy eyebrows, deep set eyes with long lashes, hypertelorism, and a broad nasal bridge. Except for hip dysplasia, no congenital malformations were detected. By conventional cytogenetics a derivative chromosome 3 de novo was diagnosed which was identified as tandem dup(3)(q12q23) by fluorescence in situ hybridization (FISH) applying arm specific paints and eight different YAC-probes.

Mosaic tetrasomy 14pter-q13 due to a supernumerary isodicentric derivate of proximal chromosome 14q.

Tetrasomy of proximal 14q is an extremely rare condition and has never been reported to be associated with survival. We here report on the first case of mosaic tetrasomy of 14pter-q13 due to a de-novo supernumerary pseudoisodicentric chromosome in a 2-year-old boy with multiple dysmorphisms and malformations. The marker was detectable in nearly 25% of lymphocytes as well as in cells from buccal mucosa.

Pathogenesis of conjunctival petechiae.

Conjunctival petechiae from 15 cases (cause of death: different natural and unnatural) were analysed using confocal laser scanning microscopy (CLSM) in order to visualize the kind of the damage within the vessel wall (diapedesis versus rhexis). The pathomorphological findings with multiple ruptures of vessels appearing to be filled to bursting point define the conjunctival petechiae as a rhexis-haemorrhage.

Cryptic chromosomal aberrations leading to an AML1/ETO rearrangement are frequently caused by small insertions.

The translocation t(8;21)(q22;q22), which results in the fusion of the AML1 (RUNX1) and ETO (CBFA2T1) genes, is a recurrent aberration in acute myeloid leukemia (AML), preferentially correlated with FAB M2, and has the highest incidence in childhood AML. Because of the favorable prognosis, the evidence of the t(8;21) or the AML1/ETO fusion gene is mandatory in most of the therapy trials, allowing the stratification of the patients to the correct risk group in terms of treatment. Here we present six out of 59 children with AML who were positive for AML1/ETO by RT-PCR, but showed no evidence of the classical t(8;21)(q22;q22) by conventional cytogenetics.

Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma.

PIK3CA, encoding the catalytic subunit p110alpha of phosphatidylinositol 3-kinase (PI3K), is activated in malignant diseases. However, the role of the PIK3CA gene aberrations for tumourigenesis of head and neck squamous cell carcinoma (HNSCC) is to date unclear. The present study was designed to determine the genomic aberration of PIK3CA in invasive HNSCC and dysplastic precursor lesions by fluorescence in situ hybridization (FISH) with a YAC probe, containing the PIK3CA gene, on isolated interphase nuclei from histomorphologically well-defined regions of formalin-fixed tissue sections and to compare these data with protein and mRNA expression of p110alpha.

Visualization of postmortem chondrocyte damage by vital staining and confocal laser scanning 3D microscopy.

The present study was designed to investigate whether the combination of vital dyes [calcein acetomethyl ester and ethidium homodimer (LIVE/DEAD Viability/Cytoxicity Kit)] together with confocal laser scanning 3D microscopy was a suitable process to detect postmortem chondrocyte damage, and whether this process could be used to establish postmortem interval. Human knee cartilage from 13 autopsies (postmortem interval from 1 day to 2.5 months) was incubated with the two dyes.