Analysis of NOTCH1 mutations as predictive biomarker for transformation in patients with follicular lymphoma: a 10-year observational retrospective cohort study

Abstract

BACKGROUND Follicular lymphoma is the most common indolent NHL in the western world. As it is an indolent lymphoma, the typical clinical practice is to only offer treatment when patients develop symptoms or when a high tumour burden is present. The prognosis of FL is partially determined by the risk of histological transformation to an agressive lymphoma (30% transformation rate at 15-y of follow-up). Recent studies have suggested that early treatment with rituximab could reduce the risk of transformation. The question that arises is which patients present a higher risk of transformation and consequently, which patients will benefit from early treatment of their lymphoma. At this time there are no predictive biomarkers to identify this subset of patients. Some studies have identified mutations in the NOTCH1 gene as a risk factor for transformation of other indolent lymphomas and therefore we presume it could be a predictive biomarker of transformation of FL at diagnosis. OBJECTIVE To analize the relationship between the mutational status of the NOTCH1 gene and the risk of transformation in patients with non-transformed follicular lymphoma at the time of diagnosis. METHODS The study is designed as a 10-year observational retrospective cohort of patients from ICO Girona-Hospital Dr. Josep Trueta in which 224 cryopreserved samples of non-transformed FL will be analyzed for the presence of NOTCH1 mutations. Posteriorly, we will assess what percentage of mutated and wild-type NOTCH1 cases suffered transformation