• New gene responsible for familial melanoma discovered

    March 28, 2014

    The research, published in the Nature Genetics journal, has been conducted by an international team in which scientists from the University of Oviedo participated. This new discovery reinforces the idea that very different types of tumors may be treated with the same drugs if they share the same mutations.

    Víctor Quesada and Andrew Ramsay in one of the laboratories of the University of Oviedo.

    A research published on March 30 by the Nature Genetics has led to the discovery that a molecular mechanism previously described by Spanish researchers and involved in the development of chronic lymphocytic leukemia is also responsible for the development of familial forms of melanoma.

    This research, coordinated by Dr. David Adams from the Wellcome Trust Sanger Institute of the United Kingdom, and which has had the collaboration of researchers Andrew Ramsay, Víctor Quesada y Carlos López-Otín, from the University Institute of Oncology of the University of Oviedo, has studied families with several cases of melanoma and has found variants of the POT1 gene present exclusively in those who suffer from the illness and absent from those who do not.

    "This discovery reinforces the immense value of projects that study the genomes of cancer to identify genes whose implication in the disease was unknown until now, and whose mutations may contribute to the development of tumors as different as melanoma or leukemia", comments López-Otín, who also adds: "These results point once again to the future of tumoral treatments depending primarily on the genetic changes that they present and not so much on the tissues in which they originate".

    The gene on which the research was focused, POT1, is involved in the protection of the telomeres -the endings of chromosomes- and has been already described by the Spanish Consortium for the Study of Cancer Genomes as one of the most frequently-mutated genes in chronic lymphocytic leukemia.

    The newly-published research was born from an observation made last year by researchers from the Spanish Consortium for the Study of the Genome of Chronic Lymphocytic Leukemia directed by Drs. Carlos López-Otín and Elías Campo. This previous study had proved the frequent existence of this type of leukemia due to mutations of POT1, involved in the protection of the endings of chromosomes, called telomeres. Researchers then thought about the possibility of other types of tumors having alterations in this same gene. In this context, researchers from European, Australian and North American institutions focused on the study of the malign skin melanoma, and more precisely on the familial forms of this disease. This type of tumors is very agressive and has a great medical relevance in countries with intense sunlight.

    The study conducted on numerous families that suffered from this disease has led to the discovery of constituing variants in the POT1 gene that are present exclusively in patients of familial melanoma, but not on members of the same families that have not developed the disease. These constituing variants, unlike somatic mutations, are not acquired during the tumoral process, but rather they exist beforehand on all the cells of the individual and may facilitate the developement of certain types of cancer. The discovery of the new gene responsible for familial tumors has immediate clinical implications, since it allows for an early diagnosis of the chances of an individual to develop said tumors.

    According to Andrew Ramsay, first co-author of the article alongside Carla D. Robles, Mark Harland and Lauren G. Aoude, "after the discovery of several variants of the POT1 gene in familial melanomas, we were able to prove that the structural and biochemical consequences of said variants on the protein codified by this gene were indistinguishable from those that we had found in the case of the somatic mutations associated to leukemia". This fact suggests that the function lost in both cases is necessary to maintain the normal state of the cells and to avoid the development of several types of tumors. Therefore, it is probable that other proteins that collaborate to the same function are also involved in the tumoral progression, and that they may relate cases that were, at first, considered unrelated. Thus, Víctor Quesada points out that "if this hypothesis was verified, it would suppose an important step towards understanding how certain types of tumors that are very hard to study now are born".


    • This research has found variants of the POT1 gene that may lead to the inheritance of a type of melanoma.
    • POT1 is a necessary factor for the proper functioning of the complex that protects the telomeres that maintains the integrity of the chromosomes.
    • The variants found are equivalent to the mutations previously identified in patients of chronic lymphocytic leukemia.
    • The mutations of POT1 seem to be part of one of the basic mechanisms that lead to the development of cancer.

    Institutions that have participated in this research:

    • University of Oviedo/University Institute of Oncology
    • Wellcome Trust Sanger Institute (Cambridge, United Kingdom)
    • QIMR Berghofer Medical Research Institute (Brisbane, Australia)
    • National Cancer Institute (Bethesda, USA)
    • Leiden University Medical Centre (Leiden, Holland)

    Funding: The work conducted by the University of Oviedo has been funded by the Ministry of Economics and Competitiveness/Carlos III Institute, the Botín Foundation and the Cajastur Social Foundation.

    Banner Image

    The image shows that the new variants of POT1 found in patients with familial melanoma are located at the same regions that the mutations previously described in leukemias. The figure represents the structure of POT1 (green) merged with the telomeric DNA (blue). The mutated zones in LLC, all of them close to telomerica DNA, are marked in orange. The new variants, marked in red, are also found new the DNA of the telomere and have similar biological consequences.