Researchers from the Catalan Institute of Oncology (IDIBELL), led by Dr Laura Valle, in collaboration with the Group on Genomic Instability and DNA Repair of the UAB Department of Genetics and Microbiology, headed by Prof Jordi Surrallés, has identified mutations in the gene FAN1 that cause hereditary colorectal cancer. An exhaustive study of one family, followed by the analysis of the gene in over 175 high-risk families, and the functional study of the mutations identified, provided proof of the causal relationship between the gene and cancer aggregation in the mutation-carrying families, which accounts for up to 3% of high-risk families.
The gene FAN1 encodes a protein involved in DNA repair that is part of the molecular pathway of Fanconi Anaemia – a pathway classically associated with breast cancer. However, FAN1 shows distinct characteristics that differentiate it from other Fanconi Anaemia genes and it interacts with proteins of the DNA mismatch repair system, whose genes, when mutated, cause hereditary colorectal cancer or Lynch syndrome.
The identification of mutations in genes associated with the predisposition to develop cancer in certain families facilitates the clinical management of these families and allows early detection and even prevention of certain types of tumours in carriers of the causal mutation. However, many of the high-risk families do not have mutations in the known genes, thus making it essential to identify new genes that cause this inherited cancer risk.
Also participating in this study were researchers from the Department of Biochemistry and Molecular Biology of the University Institute of Oncology of the Principality of Asturias, the Structural Biology and Biocomputing Programme of the Spanish National Cancer Research Centre, and other groups from the Bellvitge Biomedical Research Institute and the Catalan Institute of Oncology. Other Spanish familial cancer units and research groups were also involved in the project.
The study has been published in the September issue of the journal Gastroenterology, with Leonardo Mina, from Prof Jordi Surrallés’ group, as co-first author. The other co-first author of the article, Dr Núria Seguí, designed the cover for the journal issue.
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