title: TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding domains of TP53 predict poor outcome.
abstract: The aim of this study was to clarify whether specific p53 mutations may have biological relevance in terms of disease relapse or death in gastric carcinomas (GC). Resected specimens from a consecutive series of 62 patients with GC undergoing potentially curative surgery were prospectively studied. The mutational status of exons 5-8 of the p53 gene was investigated in 62 cases using the PCR-SSCP and sequencing. Presence of microsatellite instability (MSI) was evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%) occurred in highly conserved domains. According to the p53 specific functional domains: 4/20 mutations (20%) were in the L3 loop and 3/20 (15%) in LSH motif. Eight of the 56 GC resulted MSI-H, 5 (9%) MSI-L, and 43 (77%) MSI stable (MSS). None of the 8 (14%) MSI-H GC showed p53 mutations. p53 mutations were associated with intestinal histotype. Moreover, specific mutations in functional domain (L3 and LSH), together with advanced TNM stage, node involvement, depth of invasion, diffuse histotype, proved to be significantly related to quicker relapse and to shorter overall survival. Specific mutations in p53 functional domains, rather than any mutations in this gene, may be biologically more significant in terms of patients outcome, indicating that these mutations might have biological relevance to identify subgroups of patients at higher risk of relapse or death who might benefit from a more aggressive therapeutic approach.
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Palermo, Palermo, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Migliavacca
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.forename: Valentina
authors.initials: V
authors.lastname: Agnese
authors.forename: Simona
authors.initials: S
authors.lastname: Corsale
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Ramona
authors.initials: R
authors.lastname: Lupi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dardanoni
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Valerio
authors.forename: Gianni
authors.initials: G
authors.lastname: Pantuso
authors.forename: Gaetana
authors.initials: G
authors.lastname: Di Fede
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Tomasino
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D017677:Age Distribution; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011446:Prospective Studies; D017434:Protein Structure, Tertiary / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm