In silico analysis of a SLC6A4 G100V mutation in lung cancers.

SLC6A4 is a serotonin re-uptake transporter which has been a target for anti-depressant therapies but recently some mutations have been described in cancer cells. Here, we characterize mutations in SLC6A4 that appear in cancer cells. We employed several validated computational and artificial intelligence algorithms to characterize the mutations. We identified a previously uncharacterized G100V mutation in lung cancers. In sillico structural analysis reveals that this mutation may affect SLC6A4 ligand binding and subsequently its function. We also identified several other mutations that may affect the structure of the protein. This preliminary analysis highlights the role of SLC6A4 in human cancers.

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database.

Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survival. Here, we investigated the genetic background of IDH1-mutant gliomas using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. In astrocytoma patients, we found that IDH1 is often co-mutated with TP53, ATRX, AMBRA1, PREX1, and NOTCH1, but not CHEK2, EGFR, PTEN, or the zinc finger transcription factor ZNF429. The majority of the mutations observed in these genes were further confirmed to be either drivers or pathogenic by the Cancer-Related Analysis of Variants Toolkit (CRAVAT). Gene expression analysis showed down-regulation of DRG2 and MSN expression, both of which promote cell proliferation and invasion. There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.

Comprehensive Analysis of MEN1 Mutations and Their Role in Cancer.

MENIN is a scaffold protein encoded by the MEN1 gene that functions in multiple biological processes, including cell proliferation, migration, gene expression, and DNA damage repair. MEN1 is a tumor suppressor gene, and mutations that disrupts MEN1 function are common to many tumor types. Mutations within MEN1 may also be inherited (germline). Many of these inherited mutations are associated with a number of pathogenic syndromes of the parathyroid and pancreas, and some also predispose patients to hyperplasia. In this study, we cataloged the reported germline mutations from the ClinVar database and compared them with the somatic mutations detected in cancers from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We then used statistical software to determine the probability of mutations being pathogenic or driver. Our data show that many confirmed germline mutations do not appear in tumor samples. Thus, most mutations that disable MEN1 function in tumors are somatic in nature. Furthermore, of the germline mutations that do appear in tumors, only a fraction has the potential to be pathogenic or driver mutations.