Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/ MTUS1 in hepatocellular carcinoma

A high frequency of allelic loss affecting chromosome 8p and a minimal region of deletion at p21-22 have been previously reported in hepatocellular carcinoma (HCC), suggesting that at least one tumor suppressor gene is present in this region. In this study, we assessed whether the angiotensin II AT2...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2006-06, Vol.252 (1), p.207-215
Main Authors: Di Benedetto, M., Pineau, P., Nouet, S., Berhouet, S., Seitz, I., Louis, S., Dejean, A., Couraud, P.O., Strosberg, A.D., Stoppa-Lyonnet, D., Nahmias, C.
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
ATIP3
Base Sequence
Biochemistry, Molecular Biology
Cancer
Carcinoma, Hepatocellular - genetics
Cell Line, Tumor
Chromosome 8p22
Chromosome Mapping
Chromosomes, Human, Pair 8
DNA Mutational Analysis
DNA, Neoplasm - genetics
Genes, Tumor Suppressor
Genetic Variation
Genomics
Hepatocellular carcinoma
Human health and pathology
Humans
Hépatology and Gastroenterology
Life Sciences
Liver Neoplasms - genetics
Molecular Sequence Data
MTUS1
Polymerase Chain Reaction
Polymorphism, Genetic
RNA Splicing
Tumor suppressor gene
Tumor Suppressor Proteins - genetics
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Summary:A high frequency of allelic loss affecting chromosome 8p and a minimal region of deletion at p21-22 have been previously reported in hepatocellular carcinoma (HCC), suggesting that at least one tumor suppressor gene is present in this region. In this study, we assessed whether the angiotensin II AT2 receptor interacting protein ( ATIP)/mitochondrial tumor suppressor gene ( MTUS1), a gene newly identified at position 8p22, may be a candidate tumor suppressor gene mutated in HCC. We searched for alterations in the 17 coding exons of ATIP/ MTUS1 by means of denaturating high-performance liquid chromatography and sequencing, in 51 HCC tumors and 58 cell lines for which loss of heterozygosity status was known. Five major nucleotide substitutions were identified, all located in exons used by the ATIP3 transcript which is the only ATIP transcript variant expressed in liver. These nucleotide variations result in amino-acid substitution or deletion of conserved structural motifs (nuclear localisation signal, polyproline motif, leucine zipper) and also affect exonic splicing enhancer motifs and physiological splice sites, suggesting potential deleterious effects on ATIP3 function and/or expression.
ISSN:0303-7207
1872-8057
0303-7207
DOI:10.1016/j.mce.2006.03.014