Analysis of extended genomic rearrangements in oncological research.

Screening for genomic rearrangements is a fundamental task in the genetic diagnosis of many inherited disorders including cancer-predisposing syndromes. Several methods were developed for analysis of structural genomic abnormalities, some are targeted to the analysis of one or few specific loci, others are designed to scan the whole genome. Locus-specific methods are used when the candidate loci responsible for the specific pathological condition are known. Whole-genome methods are used to discover loci bearing structural abnormalities when the disease-associated locus is unknown. Three main approaches have been employed for the analysis of locus-specific structural changes. The first two are based on probe hybridization and include cytogenetics and DNA blotting. The third approach is based on PCR amplification and includes microsatellite or single nucleotide polymorphism (SNP) genotyping, relative allele quantitation, real-time quantitative PCR, long PCR and multiplex PCR-based methods such as multiplex ligation-dependent probe amplification and the recently developed nonfluorescent multiplex PCR coupled to high-performance liquid chromatography analysis. Whole-genome methods include cytogenetic methods, array-comparative genomic hybridization, SNP array and other sequence-based methods. The goal of the present review is to provide an overview of the main features and advantages and limitations of methods for the screening of structural genomic abnormalities relevant to oncological research

Lymphotropism of Merkel Cell Polyomavirus Infection, Nova Scotia, Canada

Lymphoid cells may be a site for virus persistence

Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development

Efficacy of rifabutin-based triple therapy as second-line treatment to eradicate helicobacter pylori infection

<p>Abstract</p> <p>Background</p> <p>Rifabutin has been found to be effective in multi-resistant patients after various treatment cycles for Helicobacter pylori (HP) infection, but it has not been analysed as a second-line treatment. Therefore, we seek to compare the effectiveness of a treatment regimen including rifabutin versus conventional quadruple therapy (QT).</p> <p>Methods</p> <p>Open clinical trial, randomised and multi-centre, of two treatment protocols: A) Conventional regime -QT- (omeprazole 20 mg bid, bismuth citrate 120 mg qid, tetracycline 500 mg qid and metronidazole 500 mg tid); B) Experimental one -OAR- (omeprazole 20 mg bid, amoxicillin 1 gr bid, and rifabutin 150 mg bid), both taken orally for 7 days, in patients with HP infection for whom first-line treatment had failed. Eradication was determined by Urea Breath Test (UBT). Safety was determined by the adverse events.</p> <p>Results</p> <p>99 patients were randomised, QT, n = 54; OAR, n = 45. The two groups were homogeneous. In 8 cases, treatment was suspended (6 in QT and 2 in OAR). The eradication achieved, analysed by ITT, was for QT, 38 cases (70.4%), and for OAR, 20 cases (44.4%); p = 0.009, OR = 1.58. Of the cases analysed PP, QT were 77.1%; OAR, 46.5%; p = 0.002. Adverse effects were described in 64% of the QT patients and in 44% of the OAR patients (p = 0.04).</p> <p>Conclusion</p> <p>A 7-day rifabutin-based triple therapy associated to amoxicillin and omeprazole at standard dose was not found to be effective as a second-line rescue therapy. The problem with quadruple therapy lies in the adverse side effects it provokes. We believe the search should continue for alternatives that are more comfortably administered and that are at least as effective, but with fewer adverse side effects.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN81058036</p

Translocation t(11;18)(q21;q21) in gastric B-cell lymphomas

Abstract Translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration reported in gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Intriguingly, this translocation has been reported only rarely in diffuse large B-cell lymphomas; it has been proposed that t(11;18)-positive tumors rarely progress to diffuse large B-cell lymphomas. We examined the frequency of chromosomal translocation t(11;18)(q21;q21) in mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma of the stomach. Paraffin-embedded tissues from patients with gastric B-cell lymphomas were selected retrospectively. The presence of the t(11;18)(q21;q21) was determined using reverse transcriptase-polymerase chain reaction and/or fluorescence in situ hybridization. beta-Actin transcript was also determined to evaluate the integrity and efficiency of RNA (cDNA) recovery from paraffin-embedded tissues. We analyzed 53 gastric B-cell lymphomas (33 diffuse large B-cell and 20 mucosa-associated lymphoid tissue) obtained from Italy, the USA, or Japan. Beta-actin transcript was amplified in 50 cases (94%), including 19 mucosa-associated lymphoid tissue and 31 diffuse large B-cell lymphomas (five with mucosa-associated lymphoid tissue components). The t(11;18) translocation was detected in 19% (6 of 31) cases with diffuse large B-cell lymphoma versus 26% (five of 19) with mucosa-associated lymphoid tissue lymphoma (P = 0.72). One of five diffuse large B-cell lymphomas with a mucosa-associated lymphoid tissue component showed the t(11;18)(q21;q21). In conclusion, translocation t(11;18)(q21;q21) was found in both mucosa-associated lymphoid tissue lymphomas and diffuse large B-cell lymphomas of the stomach at approximately equivalent frequencies; its presence does not exclude progression to diffuse large B-cell lymphoma