In July, scientists from the Hospital Clínic de Barcelona and the Universidad de Oviedo published the results of the genome sequencing of 506 patients with chronic lymphocytic leukaemia in the journal Nature. The use of this technology, which, according to Ivo Gut, has evolved more than computers themselves in the last decade, has allowed us to learn new lessons about cancer.
Chronic lymphocytic leukaemia is the most common type of leukaemia since, according to data from the Asociación Española contra el Cáncer (Spanish association against cancer), it represents 25-30% of detected cases. More than one thousand patients are diagnosed with this disease each year in Spain. The average age at the time of detection (60 years old), along with the high degree of variability in the development of the leukaemia (in some cases it evolves over a long period of time, while in others the median survival is about 5-8 years), makes this type of cancer a mystery for researchers.
Source: Ed Uthman (Wikimedia)
Knowing which genetic changes exist between the cancer cells and the healthy cells of patients could shed more light, not only on the knowledge of chronic lymphocytic leukaemia, but also on the great diversity of cancers that we are faced with. The International Cancer Genome Consortium (ICGC) was launched seven years ago with this objective in mind. It is an initiative which seeks to sequence the genome of at least 500 patients of the 50 most frequent cancers. There are currently 77 research projects in progress (the challenge of analysing the DNA of less frequent cancers, such as children’s cancers, has also been addressed). The results published in Nature are the first to decode the genetic mutations that occur in the cancer cells of patients with this type of leukaemia.
The conclusions of this research, the first of the International Cancer Genome Consortium to be completed, raise new questions in the fight against cancer. On one hand, an average of 3,000 genetic mutations per patient, which differentiate the malignant cells from the healthy cells, has been observed. Most of these changes occur in the non-coding region of the genome. This is a result that, according to Xosé S. Puente, the lead author of the publication, “also shows that one in five cases of leukaemia is caused by genetic mutations in the non-coding region of the genome”. It was first identified two years ago that a change in non-coding DNA was related to the occurrence of melanoma. Nowadays, thanks to the work carried out by Dr Carlos López Otín’s and Dr Elías Campo’s teams, it has also been possible to determine a genetic mutation in the 3’-UTR region of the NOTCH1 gene that results in a previously unknown splicing mechanism. This itself causes an increase in the activity of NOTCH1, and is related to a more aggressive development of the disease.
The research published in Nature has also discovered 12 new previously unknown genes, involved in the development of chronic lymphocytic leukaemia. This figure raises the number of genes related to the occurrence of this type of cancer to 60. In addition, mutations in an enhancer in the chromosome 9p13 cause a reduction in the expression of PAX5, a B-cell-specific transcription factor.
The results of this research, according to Puente, open the door to a new approach in medicine in the coming years. “In the future, we will start to classify patients according to their genetic profile and not so much by the location of the tumour. This will allow us to improve and personalise treatments”, indicates the scientist from the Universidad de Oviedo. His conclusions are the first reached by a team from the International Cancer Genome Consortium, which is looking to apply DNA sequencing in the fight against cancer.