Abstract
As genomic deletion in chromosome 6 has been implicated in the pathogenesis of adenoid cystic carcinoma (ACC), we assayed 58 paired normal and tumor samples for loss of heterozygosity (LOH) using 38 microsatellite markers spanning chromosome 6. Genetic loss occurred in 57% of cases, with the greatest loss found within a 10cM region flanked by markers D6S471 and D6S1687. Among the heterogeneous histologic subtypes of salivary gland carcinomas, only salivary duct carcinoma had a similar frequency of deletion in this region. This locus contains two major candidate tumor suppressor genes, PLAGL1 and LATS1. We analyzed the sequence of these genes in clinical samples of ACC, but found no tumor-specific mutations. Analysis of gene expression showed no substantial differences between samples of normal salivary gland and ACC, eliminating the most obvious candidate genes in this locus as tumor suppressors in ACC.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Carcinoma, Adenoid Cystic / genetics*
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Carcinoma, Adenoid Cystic / metabolism
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Carcinoma, Adenoid Cystic / pathology
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Chromosome Deletion*
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Chromosomes, Human, Pair 6*
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Female
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Genes, Tumor Suppressor*
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Humans
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Immunohistochemistry
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Loss of Heterozygosity
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Male
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Middle Aged
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Salivary Ducts / metabolism*
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Salivary Ducts / pathology
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Salivary Gland Neoplasms / genetics*
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Salivary Gland Neoplasms / pathology
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Sequence Analysis, DNA
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Cell Cycle Proteins
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PLAGL1 protein, human
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Transcription Factors
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Tumor Suppressor Proteins
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LATS1 protein, human
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Protein Serine-Threonine Kinases