Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma

Autor: Baldinu, Paola, Cossu, Antonio, Manca, Antonella, Satta, Maria P., Pisano, Marina, Casula, Milena, Dessole, Salvatore, Pintus, Adriana, Tanda, Francesco, Palmieri, Giuseppe
Rok vydání: 2002
Předmět:
PTEN
Cancer Research
hMSH2
polymerase chain reaction
Loss of Heterozygosity
medicine.disease_cause
Carcinoma Endometrio
Loss of heterozygosity
Analisi mutazionale
Aged
80 and over
biology
Nuclear Proteins
Middle Aged
Prognosis
Immunohistochemistry
Neoplasm Proteins
DNA-Binding Proteins
MutS Homolog 2 Protein
PCR
Oncology
Female
DNA mismatch repair
MutL Protein Homolog 1
immunoistochimica
Adult
mutational analysis
congenital
hereditary
and neonatal diseases and abnormalities
Tumor suppressor gene
endometrial carcinoma
hMLH1
Germline mutation
Proto-Oncogene Proteins
Carcinoma
medicine
Humans
neoplasms
Adaptor Proteins
Signal Transducing
Aged
Tumor Suppressor Proteins
PTEN Phosphohydrolase
nutritional and metabolic diseases
Microsatellite instability
Microsatelliti
medicine.disease
Molecular biology
Phosphoric Monoester Hydrolases
digestive system diseases
Endometrial Neoplasms
Mutation
biology.protein
Carrier Proteins
Carcinogenesis
Microsatellite Repeats
Zdroj: Cancer
94 (2002): 3157–3168. doi:10.1002/cncr.10606
info:cnr-pdr/source/autori:Baldinu, Paola; Cossu, Antonio; Manca, Antonella; Satta, Maria P.; Pisano, Marina; Casula, Milena; Dessole, Salvatore; Pintus, Adriana; Tanda, Francesco; Palmieri, Giuseppe; Palmieri, Giuseppe/titolo:Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma/doi:10.1002%2Fcncr.10606/rivista:Cancer (Print)/anno:2002/pagina_da:3157/pagina_a:3168/intervallo_pagine:3157–3168/volume:94
ISSN: 1097-0142
0008-543X
DOI: 10.1002/cncr.10606
Popis: BACKGROUND Microsatellite instability (MSI) is due mostly to a defective DNA mismatch repair (MMR). Inactivation of the two principal MMR genes, hMLH1 and hMSH2, and the PTEN tumor suppressor gene seems to be involved in endometrial tumorigenesis. In this study, Sardinian patients with endometrial carcinoma (EC) were analyzed to assess the prevalence of both the mutator phenotype (as defined by the presence of MSI and abnormal MMR gene expression at the somatic level) and the hMLH1, hMSH2, and PTEN germline mutations among patients with MSI positive EC. METHODS Paraffin embedded tissue samples from 116 consecutive patients with EC were screened for MSI by polymerase chain reaction-based microsatellite analysis. Immunohistochemistry (IHC) with anti-hMLH1 and anti-hMSH2 antibodies was performed on MSI positive tumor tissue sections. Germline DNA was used for mutational screening by denaturing high-performance liquid chromatography analysis and automated sequencing. RESULTS Thirty-nine patients with EC (34%) exhibited MSI; among them, 25 tumor samples (64%) showed negative immunostaining for hMLH1/hMSH2 proteins (referred to as IHC negative). No disease-causing mutation within the coding sequences of the hMLH1/hMSH2 and PTEN genes was found in patients with EC who had the mutator phenotype (MSI positive and IHC negative), except for a newly described hMLH1 missense mutation, Ile655Val, that was observed in 1 of 27 patients (4%). Although MSI was more common among patients with advanced-stage EC and increased as the tumor grade increased, no significant correlation with disease free survival or overall survival was observed among the two groups (MSI positive or MSI negative) of patients with EC. CONCLUSIONS In patients with MSI positive EC, epigenetic inactivations rather than genetic mutations of the MMR genes seem to be involved in endometrial tumorigenesis. No prognostic value was demonstrated for MSI in patients with EC. Cancer 2002;94:3157–68. © 2002 American Cancer Society. DOI 10.1002/cncr.10606
Databáze: OpenAIRE
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