The study marks a milestone in the understanding of chronic lymphocytic leukemia, the most common leukemia in adults, as the genomes of normal and tumor cells for more than 500 patients have been sequenced, all of them in the CNAG, providing novel mechanisms involved in the development of this tumor. Cancer originates due to the progressive accumulation of mutations in the genome of normal cells. This is why seven years ago the International Cancer Genome Consortium (ICGC) was established. The main aim of this consortium was to sequence the genome of tumor cells from at least 500 patients, and do it for each of the 50 most frequent types of cancer in the world.

The Spanish-led consortium in charge of the chronic lymphocytic leukemia study has been the first team to accomplish this ambitious objective. In this work, led by Dr. Carlos Lopez-Otin, from the University of Oviedo and by Dr. Elias Campo, from Hospital Clinic, University of Barcelona, more than 60 researchers from different centers have collaborated to mine the three billion bases of each tumor genome in search of alterations responsible for the development of this disease.

Chronic lymphocytic leukemia is the most frequent leukemia in Western countries, with more than 12,000 new cases diagnosed in Europe every year. Knowing the genetic alterations present in a tumor is a fundamental step to understand cancer development and improve current treatments. This study shows that each tumor accumulates more than three thousand mutations in its genome, but only a handful of them are relevant for tumor growth. “We have been able to define 60 different genes whose mutations cause tumor initiation and development” comments Dr. Lopez-Otin. “However, the most relevant finding of this study has been the identification of mutations in regions of the genome which do not code for proteins and whose functional relevance is still hardly known”. “These regions represent 98% of our genome, but their functions are poorly understood, so they are not routinely analyzed in patients” said Dr. Xose S. Puente from the University of Oviedo, and first author of the study. “In this work, we have shown that one in every five tumors originates due to mutations in the so called dark regions of the genome, and knowing this information is essential, as they have a clear impact on the prognosis of the disease”.

The study published today confirms the utility of genome sequencing to uncover the genetic causes of cancer and to identify novel mechanisms implicated in its development, as well as to define new therapeutic approaches for its treatment.

More than 15 institutions collaborated on the Chronic Lymphocytic Leukemia Genome Project including the CNAG, which has played an essential role in the sequencing of this huge quantity of human genomes. This research was funded by the Spanish Ministerio de Economía y Competitividad through Instituto de Salud Carlos III.

Work of reference:
Non-coding recurrent mutations in chronic lymphocytic leukaemia.

Photograph: Dr. Elías Campo (IDIBAPS) by Diario Médico