Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non- Hodgkin lymphoma and multiple tumor types

Robert S. Hauptschein, Barbara Gamberi, Pulivarthi H. Rao, Ferdinando Frigeri, Luigi Scotto, V. S. Venkatraj, Gianluca Gaidano, Torin Rutner, Yvonne H. Edwards, R. S K Chaganti, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)170-186
Number of pages17
JournalGenomics
Volume50
Issue number2
DOIs
Publication statusPublished - Jun 1 1998

ASJC Scopus subject areas

  • Genetics

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    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. (1998). Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non- Hodgkin lymphoma and multiple tumor types. Genomics, 50(2), 170-186. https://doi.org/10.1006/geno.1998.5321