Analysis of and Fanconi Anemia genes in -negative Spanish breast cancer families

Autor: García, María J., Fernández, Victoria, Osorio, Ana, Barroso, Alicia, LLort, Gemma, Lázaro, Conxi, Blanco, Ignacio, Caldés, Trinidad, Hoya, Miguel, Ramón Y Cajal, Teresa, Alonso, Carmen, Tejada, María-Isabel, San Román, Carlos, Robles-Díaz, Luis, Urioste, Miguel, Benítez, Javier
Přispěvatelé: Group of Human Genetics, Spanish National Cancer Research Center (CNIO), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III [Madrid] (ISC), Genetic Counseling Unit, Prevention and Cancer Control Department, Catalan Institute of Oncology (ICO), Translational Research Laboratory, Laboratory of Molecular Oncology, San Carlos University Hospital, Service of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Molecular Genetics Laboratory, Cruces Hospital, Genetics Department, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH)-Universidad de Alcalá - University of Alcalá (UAH), Oncology Department, Doce de Octubre Hospital
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: Breast Cancer Research and Treatment
Breast Cancer Research and Treatment, Springer Verlag, 2008, 113 (3), pp.545-551. ⟨10.1007/s10549-008-9945-0⟩
ISSN: 0167-6806
1573-7217
DOI: 10.1007/s10549-008-9945-0⟩
Popis: International audience; Recent reports have shown that mutations in the and Fanconi Anemia (FA) genes confer a moderate breast cancer risk. Discussion has been raised on the phenotypic characteristics of the associated families and tumors. The role of in breast cancer susceptibility has not been tested to date. Likewise mutation frequency has not been studied in Spanish population. We analyzed the complete coding sequence and splicing sites of and in 95 index cases of -negative Spanish breast cancer families. We also performed an exhaustive screening of three previously described rare but recurrent mutations in 725 additional probands. Pathogenic changes were not detected in . We found a novel truncating mutation c.1056_1057delGA (p.K353IfsX7) in one of the 95 screened patients, accounting for a mutation frequency of 1% in our series. Further comprehensive screening of the novel mutation and of previously reported rare but recurrent mutations did not reveal any carrier patient. We report the first example of LOH occurring in a -associated tumor. Our results rule out a major contribution of to hereditary breast cancer. Our data are consistent with the notion of individually rare mutations, lack of mutational hot-spots in the gene and existence of between-population disease-allele heterogeneity. We show evidence that loss of function might also conform to the inactivation model of a classic tumor-suppressor gene and present data that adds to the clinically relevant discussion about the existence of a -breast cancer phenotype.
Databáze: OpenAIRE
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