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

Autor: Clara Nahmias, Anne Dejean, P.O. Couraud, M. Di Benedetto, Simon N S Louis, I. Seitz, Arthur Donny Strosberg, Pascal Pineau, S. Berhouet, S. Nouet, Dominique Stoppa-Lyonnet
Přispěvatelé: Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Oncologique, Institut Curie [Paris], This work was supported by the Centre National de la Recherche Scientifique, the Institut National pour la Santé et la Recherche Médicale, the Université Paris V-René Descartes, as well as by grants from the Association pour la Recherche contre le Cancer, the Ligue contre le Cancer, the Ligue Contre le Cancer-Comité Ile de France. MdB was supported by a grant from Hybrigenics, SA (Paris, France). SL was supported by a grant from the Centre International de la Recherche contre le Cancer (CIRC) and SN was supported by a fellowship from the Association pour la Recherche contre le Cancer (ARC)., We gratefully acknowledge Aurélie Robin for excellent technical assistance, and Drs. J. Gioanni and J.L. Fischel (Centre Lacassagne, Nice, France) for kindly providing the cancer cell lines CAL33, CAL165 and CAL166., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2006
Předmět:
Hepatocellular carcinoma
MESH: Tumor Suppressor Proteins / genetics
DNA Mutational Analysis
Exonic splicing enhancer
MESH: Base Sequence
Biochemistry
Polymerase Chain Reaction
Loss of heterozygosity
Exon
0302 clinical medicine
Endocrinology
MESH: DNA
Neoplasm / genetics
MESH: Liver Neoplasms / genetics
ATIP3
MESH: Animals
Genes
Tumor Suppressor
Tumor suppressor gene
MESH: Genetic Variation
MESH: DNA Mutational Analysis
0303 health sciences
Liver Neoplasms
Chromosome Mapping
DNA
Neoplasm
Candidate Tumor Suppressor Gene
MESH: Amino Acid Substitution
MTUS1
030220 oncology & carcinogenesis
RNA splicing
Chromosomes
Human
Pair 8
MESH: Cell Line
Tumor
Carcinoma
Hepatocellular
RNA Splicing
Molecular Sequence Data
MESH: Chromosomes
Human
Pair 8
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
03 medical and health sciences
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Cell Line
Tumor
MESH: Polymorphism
Genetic
Animals
Humans
Molecular Biology
Gene
030304 developmental biology
MESH: Humans
MESH: Molecular Sequence Data
Polymorphism
Genetic
Base Sequence
Tumor Suppressor Proteins
MESH: Carcinoma
Hepatocellular / genetics
Genetic Variation
MESH: Polymerase Chain Reaction
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Molecular biology
Angiotensin II
MESH: Genes
Tumor Suppressor
Amino Acid Substitution
Cancer research
Chromosome 8p22
MESH: Chromosome Mapping
MESH: RNA Splicing
Zdroj: Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology, Elsevier, 2006, 252 (1-2), pp.207-215. ⟨10.1016/j.mce.2006.03.014⟩
Molecular and Cellular Endocrinology, 2006, 252 (1-2), pp.207-215. ⟨10.1016/j.mce.2006.03.014⟩
ISSN: 0303-7207
DOI: 10.1016/j.mce.2006.03.014⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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