Homozygous Deletions Define a Region of 8p23.2 Containing a Putative Tumor Suppressor Gene

doi:10.1006/geno.1999.6020

Genomics

Volume 62, Issue 2, 1 December 1999, Pages 184-188

https://doi.org/10.1006/geno.1999.6020 Get rights and content

Abstract

Loss of heterozygosity at microsatellite loci in chromosomal band 8p23.2 is a frequent event in squamous cell carcinomas of the head and neck, suggesting that this region contains a putative tumor suppressor. Allelic loss studies on laryngeal and oral/oropharyngeal tumors have restricted the size of this region to ∼1 cM. A similar pattern of deletions is also observed in prostatic and ovarian adenocarcinomas. As part of an effort to identify this gene by positional cloning, we developed a physical contig consisting of 12 overlapping bacterial artificial chromosome (BAC) clones spanning this interval. We developed sequence-tagged sites from the ends of these BACs and used them, along with seven microsatellite loci, to detect and map homozygous deletions in four head and neck squamous cancer cell lines. Our mapping analysis further restricted the consensus minimal region of deletion to a <191-kb interval.

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Cited by (18)

Transfer of chromosome 8 into two breast cancer cell lines: Total exclusion of three regions indicates location of putative in vitro growth suppressor genes
2003, Cancer Genetics and Cytogenetics
Loss of heterozygosity (LOH) of the short arm of chromosome 8 occurs frequently in breast tumors. Fine mapping of the smallest regions of overlap of the deletions indicates that multiple tumor suppressor genes may be located in this region. We have performed microcell-mediated chromosome transfer of chromosome 8 into two breast cancer cell lines, 21MT-1 and T-47D. Twenty-two of the resulting hybrids were characterized extensively with chromosome 8 microsatellite markers and a subset were assayed for growth in vitro and soft agar clonicity. There was no evidence in any of the hybrids for suppression of growth or clonicity that could be attributed to the presence of particular regions of chromosome 8; however, none of the 22 hybrids examined had taken up all of the donor chromosome 8, and in fact there were three regions that contained only one allele of the markers genotyped in all 22 hybrids. These results are consistent with the presence of suppressor genes on the short arm of chromosome 8 causing strong growth suppression that is incompatible with growth in vitro; that is, multiple suppressor genes may exist on the short arm of chromosome 8.
The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor
2001, Cell
Telomerase activity is critical for normal and transformed human cells to escape from crisis and is implicated in oncogenesis. Here we describe a novel Pin2/TRF1 binding protein, PinX1 that inhibits telomerase activity and affects tumorigenicity. PinX1 and its small TID domain bind the telomerase catalytic subunit hTERT and potently inhibit its activity. Overexpression of PinX1 or its TID domain inhibits telomerase activity, shortens telomeres, and induces crisis, whereas depletion of endogenous PinX1 increases telomerase activity and elongates telomeres. Depletion of PinX1 also increases tumorigenicity in nude mice, consistent with its chromosome localization at 8p23, a region with frequent loss of heterozygosity in a number of human cancers. Thus, PinX1 is a potent telomerase inhibitor and a putative tumor suppressor.
Transcript map of the 8p23 putative tumor suppressor region
2001, Genomics
Cancers of the head and neck, prostate, liver, and bladder exhibit minimal regions of deletion within chromosomal band 8p23 that either overlap or map very close to one another. We previously refined a minimal region of deletion in squamous cell carcinomas to a 112-kb interval within 8p23. There seems to be only a single gene within this region that is expressed in normal upper aerodigestive tract epithelium. This candidate for the squamous cancer suppressor, CUB and sushi multiple domains-1 (CSMD1), extends into the minimal regions of deletions defined for the other types of cancer with 8p23 deletions. RT-PCR and EST data indicate that CSMD1 is also expressed in those organs,making this gene a candidate for a suppressor of multiple types of cancer. Both the sequence of the gene and the organization of the protein are highly conserved in the mouse.
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Common fragile sites (CFS) and extremely large CFS genes are targets for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma
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^☆: Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. AF162874–AF162889.

¹: To whom correspondence should be addressed. Telephone: (314) 362-7549. Fax: (314) 367-7346. E-mail: [email protected] or [email protected].

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Regular ArticleHomozygous Deletions Define a Region of 8p23.2 Containing a Putative Tumor Suppressor Gene☆

Abstract

Genomics

Cell

Cancer Genet. Cytogenet.

Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer

Cancer Res.

A physical map of 30,000 human genes

Science

A comprehensive genetic map of the human genome based on 5,264 microsatellites

Nature

Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer

Cancer Res.

Frequent allelic loss and homozygous deletion in chromosome band 8p23 in oral cancer

Int. J. Cancer

Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction fragment length polymorphisms and microsatellite polymorphisms

Oncogene

Loss of chromosome arm 8p loci in prostate cancer—Mapping by quantitative allelic imbalance

Genes Chromosomes Cancer

Regular Article
Homozygous Deletions Define a Region of 8p23.2 Containing a Putative Tumor Suppressor Gene☆