Gene Mutation Discovered for Some Blood Cancers

Mutations in the splicing factor 3B, subunit 1 (SF3B1) gene tended to be associated with a better prognosis, raising the possibility that patients could be screened for the mutation and their treatment tailored accordingly.

Geneticists involved in an International Cancer Genome Consortium (Hinxton, UK) used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in nine patients with low-grade myelodysplasia. Massively parallel sequencing enables investigators to work out the sequence order of the components of DNA in genetic material from the patient. The purpose of this is to identify any somatically acquired mutations alterations in the DNA that have occurred after birth in the cancer cells that may be responsible for driving the malignancy.

Targeted resequencing of the gene encoding RNA SF3B1 was also performed in a cohort of 2,087 patients with myeloid or other cancers. The scientists identified 64 point mutations in the nine patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among 53 of 82 patients whose disease was characterized by ring sideroblasts. The gene was also mutated in 1% to 5% of patients with a variety of other tumor types.

Further analysis showed that patients with the SF3B1 mutation had significantly better overall survival and leukemia-free survival compared to those without the mutation. This suggests that the SF3B1 mutations drive a benign form of myelodysplastic syndromes (MDS). As these mutations can be detected easily in blood samples taken from patients, it may be feasible to identify a group of MDS patients with a benign prognosis who could receive less aggressive treatment without recourse to an invasive bone marrow biopsy to look for the presence of ring sideroblasts.

Elli Papaemmanuil, PhD, postdoctoral research fellow at the Cancer Genome Project at the Wellcome Trust Genome Center (Cambridge, UK), said, “MDS diagnosis and accurate classification still remains challenging. The identification of SF3B1 and the continuous characterization of the underlying molecular mechanisms of this disease will provide useful insights that can directly inform both the understanding and clinical management of this disease.”

The study was published on September 26, 2011, in the New England Journal of Medicine (NEJM).

Related Links:
International Cancer Genome Consortium
Wellcome Trust Genome Center