The group of
Laura Valle at the Hereditary Cancer Program of the Catalan Institute of Oncology, IDIBELL, aims at identifying new genes for hereditary colon cancer. Through the application of techniques based on massively parallel sequencing to study of the coding parts of the genome, the researchers have identified causal mutations for hereditary colorectal cancer in the FAN1 gene. The exhaustive study of one family, followed by the analysis of the gene in a series of more than 175 high-risk families and the functional study of the identified mutations, have proved the causal association of FAN1 mutations with the aggregation of cancer in families, explaining up to 3% of high-risk families.
FAN1 encodes a protein involved in DNA repair that is part of the molecular pathway of Fanconi Anemia; a pathway classically associated with breast cancer. However, FAN1 shows distinct characteristics that differentiate it from other Fanconi Anemia genes. Moreover, 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 hereditary cancer facilitates the clinical management of mutation carriers and allows early detection and even prevention of certain types of tumors in carriers of the causal mutation. However, many of the high-risk families do not have mutations in the known genes, being therefore essential to identify new genes that cause this inherited cancer risk.
To develop this study, the researchers of the Hereditary Cancer Program have collaborated with researchers of the Department of Biochemistry and Molecular Biology of the Instituto Universitario de Oncología del Principado de Asturias, the Genome Instability and DNA Repair Group of the Universitat Autònoma de Barcelona, the Structural Biology and Biocomputing Program of the Spanish National Cancer Research Center, and other groups of the Institut d’Investigació Biomèdica de Bellvitge and the Catalan Institute of Oncology. Other Spanish familial cancer units and research groups have also participated in this project.
The study has been published in the September issue of Gastroenterology. The first author of the article, Nuria Seguí, has designed the cover for the journal issue.