Identification and Somatic Characterization of the Germline PTEN Promoter Variant rs34149102 in a Family with Gastrointestinal and Breast Tumors.
Genes (Basel)
; 13(4)2022 04 05.
Article
em En
| MEDLINE
| ID: mdl-35456450
ABSTRACT
Genetic variants located in non-coding regions can affect processes that regulate protein expression, functionally contributing to human disease. Germline heterozygous mutations in the non-coding region of the PTEN gene have been previously identified in patients with PTEN hamartoma tumor syndrome (PHTS) diagnosed with breast, thyroid, and/or endometrial cancer. In this study, we report a PTEN promoter variant (rs34149102 A allele) that was identified by direct sequencing in an Italian family with a history of gastroesophageal junction (GEJ) adenocarcinoma and breast cancer. In order to investigate the putative functional role of the rs34149102 A allele variant, we evaluated the status of PTEN alterations at the somatic level. We found that PTEN protein expression was absent in the GEJ adenocarcinoma tissue of the index case. Moreover, we detected the occurrence of copy number loss involving the PTEN rs34149102 major C allele in tumor tissue, revealing that the second allele was somatically inactivated. This variant is located within an active regulatory region of the PTEN core promoter, and in silico analysis suggests that it may affect the binding of the nuclear transcription factor MAZ and hence PTEN expression. Overall, these results reveal the functional role of the PTEN promoter rs34149102 A allele variant in the modulation of PTEN protein expression and highlight its contribution to hereditary cancer risk.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Cuidados_paliativos
/
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Hamartoma Múltiplo
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Neoplasias da Mama
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Adenocarcinoma
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália