Chemical complementarity between immune receptors and cancer mutants, independent of antigen presentation protein binding, is associated with increased survival rates.

Uterine cancer has been associated with a T-cell immune response that leads to increased survival. Therefore, we used several bioinformatics approaches to explore specific interactions between T-cell receptor (TCR) and tumor mutant peptide sequences. Using endometrioid uterine cancer exome files from the The Cancer Genome Atlas database, we obtained tumor resident V-J recombinations for the T-Cell Receptor alpha gene (TRA). The charged-based, chemical complementarity for each patient's LRP2 or TTN mutant amino acids (AAs) and the recovered, TRA complementarity determining region-3 (CDR3) sequences was calculated, allowing a division of patients into complementary and noncomplementary groups. Complementary groups with TTN mutants had increased disease-free survival and increased expression of complement genes. Furthermore, the survival distinction based on CDR3-mutant peptide complementarity was independent of programmatically assessed HLA class II binding and was not observable based on the CDR3 AA chemical features alone. The above approach provides a potential, highly efficient method for identifying TCR targets in uterine cancer and may aid in the development of novel prognostic tools.

A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita.

Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of ≥10 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes (FBN2, MGF10, and PITX1), while the second case had a CNV in ZC4H2. Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.