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Biomedical subjects

Wan L Lam

Publications and source records attributed to Wan L Lam.

41 records · Page 3Linked to original sources

Characterization of the recurrent translocation t(1;1)(p36.3;q21.1-2) in non-Hodgkin lymphoma by multicolor banding and fluorescence in situ hybridization analysis.

Aberrations of chromosomal bands 1p36 and 1q11-q23 are among the most common chromosomal alterations in non-Hodgkin lymphoma (NHL). In this study, 16 cases of NHL showing recurrent unbalanced translocation t(1;1)(p36;q11-23) by G-band analysis were selected for further analysis. To delineate the exact breakpoints, multicolor band analysis for chromosome 1 (M-BAND1), and locus-specific fluorescence in situ hybridization (LS-FISH) using human genome designated BAC clones were performed. In all but one dicentric case, the breakpoint was determined to involve chromosomal bands 1p36.3 and 1q21.1-2. LS-FISH analysis for the TP73, MEL1, SKI, and CASP9 loci at 1p36, and the loci IRTA1, IRTA2, BCL9, AF1Q, JTB, and MUC1 at 1q21, verified the MBAND1 results and further delineated the breakpoints. In band 1p36, two hybridization patterns were observed, one involving deletions of MEL1, TP73, and SKI, but not CASP9, and the second involving a breakpoint telomeric to TP73. In region 1q21, four hybridization patterns were observed, the first involving duplication/translocation of all five genes; the second involving duplication/translocation of BCL9, AF1Q, JTB, and MUC1; the third involving duplication/translocation of AF1Q, JTB, and MUC1; and the fourth with a breakpoint telomeric to MUC1. Using an alpha-satellite probe for chromosome 1 (D1Z5), centromeric involvement in the unbalanced translocation t(1;1)(p36.3;q21.1-2) was excluded in all but the one dicentric case, that is, dic(1;1)(p36.3;q10). In conclusion, deletion of 1p36 and duplication of 1q21 through formation of an unbalanced translocation t(1;1)(p36.3;q21.1-2) is a non-random event in NHL, suggesting a deletion-duplication mechanism involved in lymphoma progression and justifying further systematic research.

Adult↗

3p14 and 9p21 loss is a simple tool for predicting second oral malignancy at previously treated oral cancer sites.

Treatment induces reactive changes that often resemble low-grade dysplasia at former oral cancer sites, complicating histopathological assessment. We tested a set of microsatellite markers shown previously to be predictive of progression for oral premalignant lesions for the ability to predict development of second oral malignancy (SOM). Sixty-eight oral leukoplakia at former cancer sites (with known outcome, 36 progressed to SOM) were evaluated for loss of heterozygosity at 19 loci on seven chromosome arms. 3p and/or 9p loss in these posttreatment leukoplakia was associated with a 26.3-fold increase in risk of developing SOM compared with those that retained both of these arms (P < 0.001), with 60% of cases with loss of heterozygosity developing SOM in 2 years. In contrast, histological diagnosis (moderate or severe dysplasia versus hyperplasia or mild dysplasia) had only a 1.7-fold increase in risk (P = 0.11). The identification of 3p and 9p loss in posttreatment lesions could serve as a simple and direct test for stratifying risk of SOM development.

Adolescent↗

Two-dimensional display and whole genome comparison of bacterial pathogen genomes of high G+C DNA content.

High-resolution comparison of bacterial genomes facilitates the identification of the genetic changes responsible for clinically relevant phenotypes. For this purpose we have established a method for the display and comparison of high G+C bacterial genomes in two dimensions. Here we describe the application of two-dimensional bacterial genomic display to resolve the genomes of Bordetella pertussis, Mycobacterium avium and Mycobacterium tuberculosis, and its utility in strain comparison and detection of insertion and substitution mutations.

Bacteria↗

An efficient method for the assessment of DNA quality of archival microdissected specimens.

There will be an increasing need of methods for assessing the suitability of specimens for genetic-based assays as DNA markers become an integral part of molecular diagnosis. The targeting of specimens for specific analyses will require the ability to rapidly screen for DNA quality. Conventional methods such as Southern analysis and gene specific-polymerase chain reaction (PCR) often require quantities of material that represent a significant portion of the specimen, especially in microdissected samples. Here we describe a novel application of a commonly used PCR-based DNA-fingerprinting technology that requires minimal quantities of DNA to simultaneously assess multiple regions throughout the genome for DNA quality. Randomly amplified polymorphic DNA (RAPD) PCR generates DNA fragments of a broad size range with the product size reflecting the degree of sample fragmentation. Fourteen DNA samples extracted from cells microdissected from seven formalin-fixed, paraffin-embedded oral cancer biopsies were assessed for DNA quality using gene-specific PCR and RAPD-PCR. Although the more conventional assay required 2-ng DNA (or 300-cell equivalents) to examine DNA quality at a single locus, RAPD-PCR provided a more informative profile of DNA quality from the same microdissected archival specimens.

Carcinoma, Squamous Cell↗

Two-dimensional bacterial genome display: a method for the genomic analysis of mycobacteria.

Annually, Mycobacterium tuberculosis is the cause of approximately three million deaths worldwide. It would appear that currently available therapies for this disease are inadequate. The identification of genes involved in mycobacterial virulence will facilitate the design of new prophylactic and therapeutic interventions. A method for high-resolution comparison of bacterial genomes has been developed to facilitate the identification of genes possibly involved in the virulence of clinically relevant mycobacteria. This 'two-dimensional bacterial genome display' (2DBGD) method utilizes two-dimensional DNA electrophoresis to separate, on the basis of size and G+C content, genomic fragments generated with different restriction endonucleases. The use of this method to identify genomic differences between species, strains and, most importantly, isogenic mutants of mycobacteria is reported. That 2DBGD can be used to identify differences resulting from either insertional mutagenesis using a gentamicin-resistance gene or from a frameshift mutation is demonstrated.

Bacterial Proteins↗