Executive Summary : | The mutational study of all the exons of NOTCH1 in 25 T-ALL samples revealed 52% mutations; of which 44% spans mutations in the hot spot exons and 16% in the rest of the exons [2 (8%) cases had mutations in both hot spots and other exons]. This is the first study in South Indian T-ALLs which explored all the exons of NOTCH1 for mutations. The study showed 7 novel mutations consist of 2 missense, 3 insertions, 1 deletion and 1 non sense mutation which leads to truncated protein. In addition, six missense mutations detected in the study were found functionally deleterious various bio informatics tools such as GVGD, Mutation Assesor, Polyphen 2.0, Provean and SNAP. The mutations found in the other exons were not of much significance on the NOTCH1 expression and activation as compared to the hot spot mutations. Few synonymous variants and intronic mutations were detected in the study but they were not functionally significant. Many T-ALL studies reported that the NOTCH1 mutations impact the prognosis of T-ALLs. Though the study did not reveal any prognostic significance in correlation with NOTCH1 mutation, the results need to be studied in the larger cohort to elucidate the frequency of whole NOTCH1 mutations and their role in the T-ALL leukemogenesis and prognosis. |