Identification Of Somatic Mutations In Brain Tumors By Exome Sequencing

The tumor is the result of the accumulation of genomic alterations while a normal cell turns into a tumor cell. The development of second-generation sequencing technology brought tumor research into the genomics era. The difficulty to obtain the brain tumor samples limited the brain tumor research progress. To understand the mechanism of the brain tumor, we carried out a preliminary study of neurofibromatosis type II and chordoma with exome sequencing respectively。Neurofibroma is a benign nerve sheath tumor, and it is called Neurofibromatosis when the Neurofibroma multiple or associated with systemic diseases and has3different types. Neurofibromatosis type2(NF2) is an autosomal dominant disorder caused by inactivation of a tumor suppressor gene NF2. We found a previously somatic nonsense mutation in the11th exon by exons sequence of NF2from a sporadic patient’s tumor and her parents’blood sample. Next we quantified the mutation frequency in patient’s blood and oral epithelial by clone sequencing. Besides, there were more somatic mutation sites in the sequencing region than expected. Then the exome of the patient’s blood and oral epithelial and her parents’oral epithelial was sequenced and we also observed that the patient’s low-frequency mutation sites were also more than her parents and the health control. By comparing patient’s and her parents’sequencing data, a de novo missense was identified in2nd exon of ORAI3(calcium release-activated calcium modulator3).ORAI3is involved in regulation of the intracellular Ca2+concentration which affects the efficiency of the DN A repair system. So we believe that this mutation affect patient’s intracellular Ca2+concentration regulation which reduce the efficiency of DNA repair systems, and result in more low-frequency mutation sites.Chordoma is a rare slow-growing, low-grade malignancy with local destruction. Most patients are sporadic while there are a small number of families have been reported in which multiple relatives have been affected. Previous research found that the expression of brachyury coding gene T gene in Chordoma cells and correlation with the tumorigenesis. In this study, the blood, the primary tumor and the relapsed tumor of a sporadic patient with skull base chordoma was genotyped and exome sequenced. No tumor-specific mutation and large structural variation was found, the somatic mutation on OR4K13(olfactory receptor, family4, subfamily K, member13) suggest that a minor clone in the primary tumor cells evolved into the relapse clone.