Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non- Hodgkin lymphoma and multiple tumor types Journal Article
| Authors: | Hauptschein, R. S.; Gamberi, B.; Rao, P. H.; Frigeri, F.; Scotto, L.; Venkatraj, V. S.; Gaidano, G.; Rutner, T.; Edwards, Y. H.; Chaganti, R. S. K.; Dalla-Favera, R. |
| Article Title: | Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non- Hodgkin lymphoma and multiple tumor types |
| Abstract: | Frequent deletions of the distal region on the long arm of chromosome 6 have been reported in multiple human tumors including B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of one or more tumor suppressor genes (TSGs) at this locus. Previously, we identified a region of minimal molecular deletion at 6q25-q27 (RMD-1) in B-NHL cases. To facilitate positional cloning efforts to identify the RMD-1 TSG(s), a yeast artificial chromosome (YAC) contig consisting of 110 clones was constructed across 6q26- q27 by sequence-tagged site/probe content mapping. The contig integrates 79 ordered markers including restriction fragment length polymorphisms, minisatellites, microsatellites, YAC-insert termini, expressed sequence tags, and known genes. It spans 34 cM and has a minimal tiling path of approximately 12 clones, covering an estimated 9-14 Mb with nearly every marker on the map showing at least double linkage to its adjacent markers. Dual-color fluorescence in situ hybridization of selected marker pairs on normal pachytene chromosome 6 further confirmed the YAC-based mappings. Utilizing a loss of constitutional heterozygosity assay in the B-NHL tumor panel, 24 additional 6q26-q27 polymorphic markers (21 mapping to the contig) further defined RMD-1 between markers D6S186 proximally and D6S227 distally. The minimal tiling path of the B-NHL RMD-1 consists of approximately 8 YAC clones, providing a size estimate of 5-9 Mb. This interval contains, in their entirety, several smaller candidate TSG critical regions previously delimited in other tumor systems. The AF-6 gene, mapping within RMD-1, revealed no mutations in a small subset of B-NHL. The deletion and physical maps presented herein provide a framework for the identification of the gene(s) involved in B-NHL as well as other malignancies and diseases mapped to this region and provide the initial reagents for large-scale genomic sequencing. |
| Keywords: | sequence analysis; gene deletion; mutation; cancer risk; neoplasms; in situ hybridization, fluorescence; gene frequency; carcinogenesis; molecular cloning; cloning, molecular; lymphoma, b-cell; nonhodgkin lymphoma; genetic susceptibility; chromosomes, human, pair 6; loss of heterozygosity; chromosome deletion; molecular probe techniques; multiple cancer; genes, tumor suppressor; chromosome 6q; gene location; kinesin; chromosome mapping; electrophoresis, gel, pulsed-field; polymorphism, restriction fragment length; myosins; humans; human; priority journal; article; minisatellite repeats; chromosomes, artificial, yeast; sequence tagged sites |
| Journal Title: | Genomics |
| Volume: | 50 |
| Issue: | 2 |
| ISSN: | 0888-7543 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1998-06-01 |
| Start Page: | 170 |
| End Page: | 186 |
| Language: | English |
| DOI: | 10.1006/geno.1998.5321 |
| PUBMED: | 9653644 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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