This is the first time that an essential gene for the protection of telomeres, the ends of chromosomes, has appeared mutated in human cancer
A study published today in the journal Nature Genetics explores a new mechanism that may contribute to the development of several tumours, including Chronic Lymphocytic Leukaemia, a type of cancer that affects more than a thousand new patients in Spain each year.
This work, led by researchers Carlos L-pez-Ot-n, from the University Institute of Oncology at the University of Oviedo; El-as Campo, from the Hospital Cl-nic/University of Barcelona; and Mar-a Blasco, the Director of the Spanish National Cancer Research Centre (CNIO), represents a significant milestone for the Spanish Consortium in the study of the Chronic Lymphocytic Leukaemia Genome.
"Chronic Lymphocytic Leukaemia is the most frequent leukaemia in Western countries," says L-pez-Ot-n, adding that, "Once the most frequent genetic and epigenetic changes in its development have been decoded, it's necessary to discover the biochemical mechanisms altered by those changes, in order to be able to improve the diagnosis and treatment of this disease."
Thus, continuing the work from previous studies led by Campo and L-pez-Ot-n published in Nature and Nature Genetics over the past two years, the researchers concentrated on the mutations affecting POT1, one of the genes involved in the protection of the ends of chromosomes, the telomeres.
This is the first time that a gene with this function has appeared mutated in a human cancer. Blasco says: "We have been studying telomere biology for a long time, given that alterations in telomere maintenance are associated with cancer and ageing. Although the mechanisms used by tumour cells to alter their telomeres have been identified, POT1 mutations reveal yet another, previously unknown route."
Each chromosome has, at its extremes, in its telomeres, a protective hood made up of proteins, and POT1 is the staple that fixes it in place, joining it to the telomeric DNA. All of the mutations discovered in POT1 prevent this gene from fulfilling its function. The DNA at the end of the chromosome is therefore left without its protective cover. The study of the biochemical pathway that leads from these abnormalities to the uncontrolled growth of B lymphocytes can provide important clues for the understanding of chronic lymphocytic leukaemia and cancer in general.
ONE OF THE MOST FREQUENTLY MUTATED GENES IN LEUKAEMIA
Furthermore, after analysing the genome of 341 chronic lymphocytic leukaemia patients -comparing for each case the genes from normal healthy cells with those of tumour cells-, researchers have discovered that POT1 is one of the most frequently mutated genes in this illness.