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1.
Am J Pathol ; 155(6): 1817-21, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10595910

ABSTRACT

Extranodal mucosa-associated lymphoid tissue (MALT)-type lymphomas and nodal and splenic marginal zone B cell lymphomas (MZBL) share morphological and immunophenotypic features with marginal zone B cells of reactive lymphoid tissues. Although displaying a similar immunophenotype, recent investigations suggest fundamental genetic differences among these subgroups. To determine the prevalence of the t(11;18) in a larger series of MALT-type lymphomas and to investigate a possible occurrence in other lymphomas, we screened 106 non-Hodgkin's lymphomas (NHL) by interphase cytogenetics using yeast artificial chromosome (YAC) probes flanking the breakpoint at 11q21. A signal constellation indicating a disruption in 11q21 and thus pointing to the presence of the t(11;18) was observed in 9 of 33 (27%) low-grade lymphomas of MALT type. The complete absence of t(11;18)-positive cells in 32 primary and secondary extranodal high-grade lymphomas suggests that low-grade lymphomas of MALT type characterized by the t(11;18) are unlikely to transform into high-grade tumors. The absence of tumor cells carrying the t(11;18) in nodal MZBL challenges the assumption that most, if not all, of these tumors represent the nodal manifestation of a so far undetected low-grade lymphoma of MALT type. The t(11;18) was not detected in a single case of 29 splenic MZBL investigated. This observation strengthens the view that splenic MZBL are biologically different from extranodal MZBL of MALT type.


Subject(s)
Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 18/genetics , Lymphoma, B-Cell, Marginal Zone/genetics , Lymphoma, B-Cell/genetics , Translocation, Genetic , Chromosome Banding , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Interphase , Lymphoma, B-Cell/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Non-Hodgkin/genetics , Lymphoma, Non-Hodgkin/pathology
2.
Genome Res ; 9(11): 1074-86, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10568747

ABSTRACT

The region p13 of the short arm of human chromosome 11 has been studied intensely during the search for genes involved in the etiology of the Wilms' tumor, aniridia, genitourinary abnormalities, mental retardation (WAGR) syndrome, and related conditions. The gene map for this region is far from being complete, however, strengthening the need for additional gene identification efforts. We describe the extension of an existing contig map with P1-derived artificial chromosomes (PACs) to cover 7.5 Mb of 11p13-14.1. The extended sequence-ready contig was established by end probe walking and fingerprinting and consists of 201 PAC clones. Utilizing bins defined by overlapping PACs, we generated a detailed gene map containing 20 genes as well as 22 anonymous ESTs which have been identified by searching the RH databases. RH maps and our established gene map show global correlation, but the limits of resolution of the current RH panels are evident at this scale. Initial expression studies on the novel genes have been performed by Northern blot analyses. To extend these expression profiles, corresponding mouse cDNA clones were identified by database search and employed for Northern blot analyses and RNA in situ hybridizations to mouse embryo sections. Genomic sequencing of clones along a minimal tiling path through the contig is currently under way and will facilitate these expression studies by in silico gene identification approaches.


Subject(s)
Chromosomes, Human, Pair 11 , Gene Expression , Animals , Bacteriophage P1/genetics , Blotting, Northern/methods , Chromosome Mapping , Chromosome Walking/methods , Chromosomes, Artificial, Yeast/genetics , Contig Mapping/methods , DNA Fingerprinting/methods , DNA Probes/genetics , DNA, Complementary/genetics , DNA, Viral/genetics , Databases, Factual , Embryo, Mammalian , Expressed Sequence Tags , Humans , In Situ Hybridization/methods , Mice , Physical Chromosome Mapping , RNA/analysis
4.
Genomics ; 53(2): 155-63, 1998 Oct 15.
Article in English | MEDLINE | ID: mdl-9790764

ABSTRACT

A large body of evidence that links alterations of chromosome 11p13 to tumor formation and various developmental disorders has been accumulated. To address the underlying genetic events it would be helpful to have a comprehensive gene map of the region, and this is most readily achieved by generating the complete genomic sequence. Building upon previous mapping and YAC contig analysis we have established a 3-Mb sequence-ready PAC contig. It was constructed by chromosome walking and independently verified by fingerprint analysis of individual clones. The contig starts from the catalase gene on the centromeric side and reaches beyond the PAX6 gene at the 11p13/p14.1 boundary. Additional smaller contigs on either side were identified, but still have to be linked up. The 3-Mb contig spans the central region of deletions encompassing 16 chromosomal breakpoints in patients with WAGR syndrome (Wilms tumor, aniridia, genitourinary malformation, mental retardation), and its construction is an important step in facilitating functional analysis of these genes.


Subject(s)
Chromosome Mapping/methods , Chromosomes, Human, Pair 11 , Cloning, Molecular/methods , Contig Mapping , Wilms Tumor/genetics , Chromosome Aberrations , DNA Fingerprinting , Gene Library , Humans , Sequence Analysis, DNA
5.
Genomics ; 30(1): 37-45, 1995 Nov 01.
Article in English | MEDLINE | ID: mdl-8595901

ABSTRACT

The WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) deletion region on chromosome 11p13 has been extensively characterized by deletion analysis and long-range restriction mapping. A dense probe set is available for this genomic region, which harbors a number of disease gene loci, some of which still are not cloned. The identification of candidates for these genes would be greatly facilitated by a complete gene map for this chromosomal segment. As an initial step toward this goal, we have isolated the entire region in 58 overlapping YAC clones. The contig spanning 8 Mb from RAG1 to KCNA4 has been assembled by STS and probe content mapping for 76 loci with an average spacing of about 100 kb. A subset of clones has been analyzed by PFG analysis to position these within the known physical map. Common microsatellite markers permit an alignment of the YAC contig with the genetic and radiation hybrid maps of chromosome 11. Ten known genes, some with much more refined map positions, are placed in the contig. The severalfold coverage of 11p13-p14.1 provides a reliable resource for the future development of a complete gene map of this region.


Subject(s)
Chromosome Mapping , Chromosomes, Artificial, Yeast/chemistry , Chromosomes, Artificial, Yeast/genetics , Chromosomes, Human, Pair 11 , Homeodomain Proteins , WAGR Syndrome/genetics , Base Sequence , Chloramphenicol O-Acetyltransferase/genetics , Cloning, Molecular/methods , DNA Probes , Databases, Factual , Gene Library , Genetic Markers , Humans , In Situ Hybridization , Molecular Sequence Data , Proteins/genetics
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