Identification of chromosomal rearrangements in colorectal cancer

Abstract

Cancer research is continuously shedding light into these worldwide leading diseases. It is mandatory to have higher knowledge in cancer biology to consequently find out new candidate biomarkers and therapeutics. Among all of them, Colorectal cancer is the most commonly seen of human malignant cancers and has the third highest mortality rate[1]. Since the release of the first human genome sequence in 2004, new techniques have revolutionised the study of genetics and its possible applications. A broad type of studies has been carried out; being Single Nucleotide Polymorphisms and Copy Number Variants the most intensively studied analysis. However, other kinds of mutations involving larger parts of the genome, the so-called structural variants, have been substantially less analyzed due to technical limitations. High-throughput sequencing methods seem to have lowered these restrictions. In this study, gene fusions have been searched in whole exome sequencing samples taking 42 paired normal and cancer tissues. Beginning with short-read files obtained with the mentioned method, they have been aligned against a reference genome to later be analyzed with Breakdancer, a structural variant calling algorithm. After some filtering criteria performed in order to remove a high proportion of false positives, a highly probable list of 22 balanced structural variants (translocations and/or inversions) has been manually studied to get a final result of 20 chromosomal rearrangements, 8 of which are considered gene fusions. In addition, it has been found that one recurrent translocation seen in recent studies is indeed a false positive. Further studies taking into account these results may contribute to the findings of new biomarkers for certain subtypes of colorectal cancer.