title: The presence of multiple regions of homozygous deletion at the CSMD1 locus in oral squamous cell carcinoma question the role of CSMD1 in head and neck carcinogenesis.
abstract: We and others previously identified a region of hemizygous or homozygous deletion at chromosome band 8p23 in oral and oropharyngeal squamous cell carcinomas (OSCCs) and many other cancer types, suggesting the presence of a tumor-suppressor gene (TSG) in this region. Recently, based on a single region of homozygous deletion in head and neck squamous cell carcinomas (HNSCC), a putative TSG, CUB and sushi multiple domains-1 (CSMD1), has been identified. In the present study, we mapped three OSCC cell lines with previously described homozygous deletions at a high resolution onto a detailed physical map. Critically, this map covered a wider region than that used in previous studies, and in contrast to these studies, our results revealed multiple regions of homozygous deletion within a small interval on 8p23. To investigate this deletion pattern further, we generated a panel of 34 sequence tagged site (STS) markers spanning the region and tested these three cell lines and an additional 34 OSCC cell lines, identifying homozygous deletions in a further four. Combining the results from all seven deleted cell lines identified three non-overlapping regions of homozygous deletion. This complex pattern could be consistent with the presence of multiple TSGs or one very large TSG in this region, and/or specific chromosomal instability. CSMD1 spans two of the three deleted regions and, therefore, would appear to be an excellent candidate for a TSG. However, deletion mapping with STSs corresponding to the exons of CSMD1 shows that some of the deletions do not interrupt its coding region, and in other cell lines the coding region is interrupted by two discontinuous homozygous deletions, suggesting the presence of redundant deletions. These results call into question whether the CSMD1 gene is the 8p23 TSG or whether this or any other genes at this locus are involved in the development of OSCC.
authors.affiliation: Department of Medical Genetics, University of Manchester, Manchester, United Kingdom.
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Andrew
authors.initials: A
authors.lastname: Jackson
authors.forename: Kristie
authors.initials: K
authors.lastname: Maguire
authors.forename: Joseph
authors.initials: J
authors.lastname: Wood
authors.forename: Susanne
authors.initials: S
authors.lastname: Gollin
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Ishwad
authors.forename: Ian
authors.initials: I
authors.lastname: Paterson
authors.forename: Steven
authors.initials: S
authors.lastname: Prime
authors.forename: Kenneth
authors.initials: K
authors.lastname: Parkinson
authors.forename: Sandra
authors.initials: S
authors.lastname: Bell
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Woods
authors.forename: Alexander
authors.initials: A
authors.lastname: Markham
authors.forename: Richard
authors.initials: R
authors.lastname: Oliver
authors.forename: Robert
authors.initials: R
authors.lastname: Woodward
authors.forename: Philip
authors.initials: P
authors.lastname: Sloan
authors.forename: Michael
authors.initials: M
authors.lastname: Dixon
authors.forename: Andrew
authors.initials: A
authors.lastname: Read
authors.forename: Nalin
authors.initials: N
authors.lastname: Thakker
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D052138:Genes, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D020161:Physical Chromosome Mapping / Q000379:methods; D012689:Sequence Homology, Nucleic Acid; D016324:Sequence Tagged Sites; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers