Identification of a Rare Germline Heterozygous Deletion Involving the Polycistronic miR-17-92 Cluster in Two First-Degree Relatives from a BRCA 1/2 Negative Chilean Family with Familial Breast Cancer: Possible Functional Implications.

de Mayo, Tomás; Ziegler, Annemarie; Morales, Sebastián; Jara, Lilian

de Mayo, Tomás; Ziegler, Annemarie; Morales, Sebastián; Jara, Lilian.

Afiliação

de Mayo T; Center for Genetics and Genomics, School of Medicine, Clinica Alemana Universidad del Desarrollo, Avenida Las Condes 12438 Lo Barnechea, 7710162 Santiago, Chile. seba.morales.p@gmail.com.
Ziegler A; Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Avenida Independencia 1027, 8380453 Santiago, Chile. seba.morales.p@gmail.com.
Morales S; Center for Genetics and Genomics, School of Medicine, Clinica Alemana Universidad del Desarrollo, Avenida Las Condes 12438 Lo Barnechea, 7710162 Santiago, Chile. aziegler@udd.cl.
Jara L; Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Avenida Independencia 1027, 8380453 Santiago, Chile.

Int J Mol Sci ; 19(1)2018 Jan 22.

Article em En | MEDLINE | ID: mdl-29361751

RESUMO

Micro-RNAs (miRNAs) have emerged as novel gene expression regulators. Recent evidence strongly suggests a role for miRNAs in a large variety of cancer-related pathways. Different studies have shown that 18.7 to 37% of all human miRNA genes are clustered. miR-17-92 polycistronic cluster overexpression is associated with human hematolymphoid and solid malignancies including breast cancer (BC). Here, we report the identification of rs770419845, a rare 6 bp deletion located within the polycistronic miR-17-92 cluster, in two first-degree relatives from a Chilean family with familial BC and negative for point mutations in BRCA 1/2 genes. The deletion was identified by Sanger sequencing when 99 BRCA1/2 mutation-negative BC cases with a strong family history were initially screened. In silico analysis predicts that rs770419845 affects the secondary structure and stability of the pre-miR-17-pre-miR-18 region and the entire 17-92 cluster. The deletion was screened in 458 high-risk BRCA1/2-negative Chilean families and 480 controls. rs770419845 was not detected in any control but identified in a single family with two cases of BC and other cancers. Both BC cases, the mother and her daughter, carried the deletion. Based on bioinformatic analyses, the location of the deletion and its low frequency, we presume rs770419845 may be a pathogenic variant. Functional studies are needed to support this hypothesis.

Assuntos

Neoplasias da Mama/diagnóstico; Neoplasias da Mama/genética; Mutação em Linhagem Germinativa; Heterozigoto; MicroRNAs/genética; Família Multigênica; Deleção de Sequência; Adulto; Idoso; Sequência de Bases; Chile; Família; Feminino; Humanos; Pessoa de Meia-Idade; Conformação de Ácido Nucleico; Linhagem; RNA Longo não Codificante; Análise de Sequência de DNA

Palavras-chave

Chilean population; deletion; familial breast cancer; miR-1792 polycistronic cluster

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Família Multigênica / Deleção de Sequência / Mutação em Linhagem Germinativa / MicroRNAs / Heterozigoto Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adult / Aged / Female / Humans / Middle aged País/Região como assunto: America do sul / Chile Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Chile País de publicação: Suíça

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