As Elías Campo explains, chronic lymphocytic leukaemia is the most frequent form of the disease in western countries, with more than one thousand patients diagnosed each year in Spain alone. In a previous study, published this year in Nature, the same team revealed the first keys to understanding the mutations leading to uncontrolled proliferation of B-lymphocytes in CLL sufferers. However, the mechanisms of tumorigenesis are highly diverse, making it necessary to sequence the tumour genomes of a large patient sample.
While it is known that cancer is produced by the accumulation of genetic damage in healthy cells, identifying the specific mutations in each case was, until recently, a lengthy and laborious process. In the new study, the team of researchers has managed to simplify the process by focusing on the exome, which comprises those parts of the genome that contain the coding regions of the genes, using cutting-edge sequencing technology at the National Center for Genome Analysis (CNAG) in Barcelona, located at the Barcelona Science Park. This approach has enabled them to study the most relevant areas of the genome by sequencing only 2 % of the 3,000 million nucleotides that make up the complete genome.
The specific mutations can be identified by comparing the exome sequence from cancer cells with the corresponding sequence in healthy cells from the same patient. According to the researchers, the approach has enabled them to pinpoint the most frequently occurring mutations in the onset of this form of leukaemia. Combined analysis of over 1000 mutated genes from the tumour cells of the 105 patients participating in the study has revealed new biochemical pathways that could prove relevant in the search for alternative treatments for CLL. The study has also detected recurrent mutations of the SF3B1 gene, involved in messenger RNA maturation, which is a crucial process in the cell cycle.
Article:
Víctor Quesada, Laura Conde, Neus Villamor, Gonzalo R. Ordóñez, Pedro Jares, Laia Bassaganyas, Andrew J. Ramsay, Sílvia Beà, Magda Pinyol, Alejandra Martínez-Trillos, Mónica López-Guerra, Dolors Colomer, Alba Navarro, Tycho Baumann, Marta Aymerich, María Rozman, Julio Delgado, Eva Giné, Jesús M. Hernández, Marcos González-Díaz, Diana A. Puente, Gloria Velasco, José M. P. Freije, José M. C. Tubío, Romina Royo, Josep L. Gelpí, Modesto Orozco, David G. Pisano, Jorge Zamora, Miguel Vázquez, Alfonso Valencia, Heinz Himmelbauer, Mónica Bayés, Simon Heath, Marta Gut, Ivo Gut, Xavier Estivill, Armando López-Guillermo, Xose S. Puente, Elías Campo y Carlos López-Otín.
«Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia»,
Nature Genetics, December 2011, doi: 10.1038/ng.1032 .
