Pangenomic Classification of Pituitary Neuroendocrine Tumors

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X chromosomal and autosomal loss of heterozygosity and microsatellite instability in human cervical carcinoma

The study analyzes tumor material and normal tissue from 27 patients with pure squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH) and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci. Overall, 4-40% of the informative cases showed LOH at autosomal regions with the highest frequency at 3p (21-40%) and a marked frequency at 2q35-q37.1 (12.5%) and 17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG) function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG. A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a regulatory function in the cell cycle via cyclin-dependent kinases. MSI was detected in autosomal regions in up to 7% in regions linked to the X chromosome in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our results and those obtained from the literature suggest that autosomal LOH and MSI in carcinomas of the cervix uteri are predominantly found at regions with putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more strongly connected to disturbances in cell cycle regulation.     

Comparative genomic hybridization (CGH) of augmentation cystoplasties

OBJECTIVE: Tumors arising within augmentation cystoplasties are aggressive, have poor prognosis and the majority are not detected at follow-up cystoscopy. Genetic changes in tumors precede morphological abnormalities. Therefore, the aim of this study was to investigate whether genetic abnormalities detected by comparative genomic hybridization (CGH) could be used to identify those patients with augmentation cystoplasties at increased risk of tumorigenesis. METHODS: Bladder biopsy samples were obtained from 16 augmentation cystoplasty patients both distant from and near to the enterovesical anastomosis. CGH was used to detect genetic abnormalities in DNA extracted from the biopsies, archival specimens of two augmentation cystoplasties and two de novo bladder adenocarcinomas. RESULTS: A greater number of amplifications on 2p, 3q, 8q, 9p, 17p, 18pq and 20pq, were observed in bladder biopsies obtained near to the enterovesical anastomosis compared to those taken distant to the suture line. CGH of archival augmentation cystoplasty tumor DNA indicated abnormalities at several loci with amplifications at 2q, 5q, 10p and 21pq, while deletions occurred at 5p and 16p. CONCLUSIONS: The results of this study suggest that the urothelium adjacent to the bladder and/or bowel anastomosis in augmentation cystoplasties is genetically unstable. Furthermore, longitudinal studies are required to establish whether or not patients exhibiting genetic instability following augmentation cystoplasty are at greater risk of developing tumors than those with genetically stable epithelia.     

Translocation t(6;14) as the Sole Chromosomal Abnormality in Adenoid Cystic Carcinoma of the Base of Tongue

We present an adenoid cystic carcinoma of the base of tongue in a 48-year-old male with a restricted chromosomal alteration by cytogenetic and spectral karyotypic analysis (SKY). SKY and G-banding analyses identified the t(6;14)(q25;q13) as the sole structural aberration in all metaphases analyzed. This finding supports a critical role for this event in the development of this tumor. The implications of chromosome 6q translocation in this case and in previously reported adenoid cystic carcinomas are highlighted and discussed.     

Molecular analysis and polymorphism of the DLA-DQB genes

Abstract: Partial-length cDNA clones and full-length genomic clones corresponding to a complete canine DQB class It gene were isolated. Southern analyses suggested the presence of two DQB genes - one of which appeared to be a pseudogene lacking exon 2 called DQB2. The other DQB gene, called DQB1, was isolated from a genomic phage clone and contained six exons. The DQB1 clone was restriction mapped, and exon 2 was sequenced from 70 dogs. Twenty alleles were found. Most of the amino acid substitutions occurred at putative positions in the peptide binding site. Inheritance of these sequences showed Mendelian segregation with one or two alleles per dog. Cluster analysis of the nucleotide and predicted amino acid sequences subdivided the canine DQB1 alleles into four major allelic groups. The number of nonsynonymous changes was higher than the number of synonymous changes in the putative antigen recognition sites suggestive of positive selection.     

Rh phenotype prediction by DNA typing and its application to practice

The complexity of the RHD and RHCE genes, which is the greatest of all blood group systems, confounds analysis at the molecular level. RH DNA typing was introduced in 1993 and has been applied to prenatal testing. PCR-SSP analysis covering multiple polymorphisms was recently introduced for the screening and initial characterization of partial D. Our objective is to summarize the accrued knowledge relevant to the approaches to Rh phenotype prediction by DNA typing, their possible applications beyond research laboratories and their limitations. The procedures, results and problems encountered are highly detailed. It is recommended that DNA typing comprises an analysis of more than one polymorphism. We discuss future directions and propose a piecemeal approach to improve reliability and cost-efficiency of blood group genotyping that may eventually replace the prevalent serology-based techniques even for many routine tasks. Transfusion medicine is in the unique position of being able to utilize the most extensive phenotype databases available to check and develop genotyping strategies.     

Molecular cytogenetic characterization of Thinopyrum and wheat--Thinopyrum translocated chromosomes in a wheat--Thinopyrum amphiploid

The wheat--Thinopyrum amphiploid 'Agrotriticum # 3425' (AT 3425), which is highly resistant to Cephalosporium stripe, was identified to carry seven pairs of Thinopyrum chromosomes, three pairs of wheat--Thinopyrum translocated chromosomes and 18 pairs of wheat chromosomes. Fluorescence genomic in situ hybridization (FGISH), C-banding, sequential C-banding and FGISH, and denaturing polyacrylamide gel electrophoresis (SDS-PAGE) were used to characterize and identify the chromosomes. The Thinopyrum chromosomes in AT 3425 were designated as T1 through T7 based on their C-banding patterns. The FGISH and C-banding patterns of mitotic chromosomes in AT 3425 and meiotic chromosomes in the hybrid between AT 3425 and wheat cultivar 'Chinese Spring' (CS) revealed that wheat chromosomes 1D, 2B and 3D were involved in the three wheat-Thinopyrum chromosome translocations designated as (W-T)1, (W-T)2, and (W-T)3 respectively. The analysis of high-molecular-weight glutenin subunits in single seeds of AT 3425 confirmed the involvement of wheat chromosome 1D in the translocation (W-T)1. The designations 1DSuu.1DL-1TL, 2BSuu.2BL-2TL and 3DSuu.3DL-3TL were suggested for the wheat--Thinopyrum translocated chromosomes (W-T)1, (W-T)2 and (W-T)3 in AT 3425 respectively.     

Comparative Analysis of Crossover Exchanges and Chiasmata in Allium Cepa × Fistulosum After Genomic In Situ Hybridization (GISH)

Genomic in situ hybridization (GISH) successfully differentiated homoeologous genomes in the interspecific hybrid Allium cepa × fistulosum, thus allowing the detection of reciprocal crossover events as label exchanges in separating anaphase I chromosomes. Three of the eight chromosome pairs were positively identified by fluorescence in situ hybridization (FISH) to rDNA sequences. There was a general similarity of the GISH-based label exchange frequencies and metaphase I chiasma frequencies, but with a 20% deficit of chiasmata. Reasons for this apparent deficit are discussed. The locations of chiasmata and label exchanges are in broad agreement.     

Hantaviruses in Central South America: phylogenetic analysis of the S segment from HPS cases in Paraná, Brazil

We sequenced the complete S segments of hantaviruses detected from 12 HPS patients living in southern of Brazil. Samples were obtained from patients diagnosed in different years, in distinct areas, and with a broad spectrum of clinical signs. Despite these differences, all the S proteins of hantavirus from Paraná were identical, except for one amino acid substitution. Phylogenetic analyses of the complete S segment nucleotide and amino acid sequences indicated that hantaviruses from Paraná form a distinct clade from those circulating in South and North America. Other hantaviruses from Brazil were not placed in the same clade. The Oligoryzomys nigripes-associated strains ITA37 and ITA38 from Paraguay were found to belong to the same clade as the hantaviruses from Paraná. Paraguay and Paraná state are located at the same latitude and some ecosystems are similar in both places. The geographic position and common rodent hosts could explain this phylogenetic relationship.     

Quantitative expansion of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas

The pathogenesis and interrelationships of neuroendocrine lung carcinomas are not well understood. Tissue macro-arrays prepared from surgical resection specimens from 35 patients with typical carcinoid (TC), six with atypical carcinoid (AC), 13 with large cell neuroendocrine carcinoma (LCNEC), and 15 with small cell lung carcinoma (SCLC) were investigated by fluorescence in situ hybridization (FISH) and immunohistochemistry. Hybridizations with locus-specific DNA probes demonstrated a high incidence of deletion for the tumour suppressor genes p53 and retinoblastoma (Rb), and for the oncogene cyclin D1, comparable in all carcinoma types. Similarly, an increase of DNA copy number for the Her-2/neu and c-myc oncogenes was noted in all neoplasms. A more detailed quantitative analysis of the results, however, demonstrated increasing numbers of cells harbouring these genomic alterations, from low-grade TC to highly malignant SCLC, with the exception of cyclin D1 deletion. Mutations of the p53 and Rb genes, as assayed by immunohistochemical studies, were observed at high incidence in high-grade carcinomas, compared with a low incidence in the low-grade carcinomas. Conversely, in all carcinoma types, neither membrane-bound Her-2/neu nor nuclear cyclin D1 was detected. It is concluded that structural genomic alterations are frequent in neuroendocrine lung carcinomas and that their occurrence may be underestimated by immunohistochemical studies alone. The quantitative expansion of the Rb, p53, c-myc, and Her-2/neu alterations towards high-grade carcinomas suggests common pathogenetic mechanisms in the spectrum of these neoplasms.