DNA sequencing identifies new altered genes that drive CLL
June 03, 2017
The SF3B1 gene was the second most commonly mutated gene, being found abnormal in 14 of the 91 leukemia DNA samples. The gene's full name is Splicing Factor 3b, subunit 1, and the protein it makes is part of the "spliceosome" - a collection of proteins that govern the splicing out of extraneous RNA molecules ("introns") to create the RNA message ("exons"), or molecular recipe, from which the cell manufactures proteins for the body.
"Defects in splicing have not previously been implicated in the biology of CLL," the researchers wrote.The researchers checked to see whether CLL samples that contained the mutated genes also had specific deletions in chromosomes (the DNA structures that carry genes) previously known to signal a poor outlook in patients. They found that, indeed, the SF3B1 gene was often found in tandem with a particular chromosomal abnormality, consistent with a more aggressive form of CLL.
However, independent of the presence of the chromosomal deletion, the study revealed that a mutated SF3B1 gene by itself was a red flag for an aggressive case of CLL; patients harboring the mutant SF3B1 gene were more likely to need treatment sooner than individuals lacking the gene. Wu said that that the gene alteration might serve as a biomarker. Since these patients have more aggressive disease, knowledge of the presence of the gene alteration might prompt physicians early on to consider alternatives to conventional chemotherapy, such as earlier use of stem cell transplants to quell the disease.
The researchers said the study findings show the value of large-scale genome searches in elucidating cancers. The numerous genetic flaws uncovered by the search could not only aid in the prediction of disease course, they said, but also offer clues to the biological underpinnings of CLL, paving the way for novel targeted treatments.
Source: Dana-Farber Cancer Institute