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Fibroblast growth factor ligands and receptors (FGF and FGFR) play critical roles in tumorigenesis, and several drugs have been developed to target them. We report the biologic correlates of FGF/FGFR abnormalities in diverse malignancies. The medical records of patients with cancers that underwent targeted next generation sequencing (182 or 236 cancer-related genes) were reviewed. The following FGF/FGFR genes were tested: FGF3, 4, 6, 7, 10, 12, 14, 19, 23 and FGFR1, 2, 3, and 4. Of 391 patients, 56 (14.3%) had aberrant FGF (N = 38, all amplifications) and/or FGFR (N = 22 including 5 mutations and one FGFR3-TACC3 fusion). FGF/FGFR aberrations were most frequent in breast cancers (26/81, 32.1%, p = 0.0003). In multivariate analysis, FGF/FGFR abnormalities were independently associated with CCND1/2, RICTOR, ZNF703, RPTOR, AKT2, and CDK8 alterations (all P < 0.02), as well as with an increased median number of alterations (P < 0.0001). FGF3, FGF4, FGF19 and CCND1 were co-amplified in 22 of 391 patients (5.6%, P < 0.0001), most likely because they co-localize on the same chromosomal region (11q13). There was no significant difference in time to metastasis or overall survival when comparing patients harboring FGF/FGFR alterations versus those not. Overall, FGF/FGFR was one of the most frequently aberrant pathways in our population comprising patients with diverse malignancies. These aberrations frequently co-exist with anomalies in a variety of other genes, suggesting that tailored combination therapy may be necessary in these patients.

We have previously shown that an 18 amino acid long peptide, named Hp91, whose sequence corresponds to a region within the endogenous protein HMGB1, activates dendritic cells (DCs) and acts as adjuvant in vivo by potentiating Th1-type antigen-specific immune responses. We analyzed the structure-function relationship of the Hp91 peptide to investigate the amino acids and structure responsible for immune responses. We found that the cysteine at position 16 of Hp91 enabled formation of reversible peptide dimmers, monomer and dimmer were compared for DC binding and activation. Stable monomers and dimers were generated using a maleimide conjugation reaction. The dimer showed enhanced ability to bind to and activate DCs. Furthermore, the C-terminal 9 amino acids of Hp91, named UC1018 were sufficient for DC binding and Circular dichroism showed that UC1018 assumes an alpha-helical structure. The ninemer peptide UC1018 induced more potent antigen-specific CTL responses in vivo as compared to Hp91 and it protected mice from tumor development when used in a prophylactic vaccine setting. We have identified a short alpha helical peptide that acts as potent adjuvant inducing protective immune responses in vivo.

Lisa M Bashore, Glenda Daniels, Lori Borchers, Lynette L Howington, Dennis J Cheek Harris College of Nursing and Health Sciences, Texas Christian University, Fort Worth, TX, USA Background: This quasi-experimental study explored full-time nurse faculty competency in genomics and genetics using a validated measure prior to and following educational sessions during one academic semester. The findings represent the researchers’ efforts to educate nurse faculty and to support their competency in genomics and genetics as information shared with students is only as robust as faculty knowledge.Methods: Faculty who consented to participate completed the Genomic Nurse Concept Inventory (GNCI©) to measure their knowledge of the concepts surrounding genomics and genetics prior to the education intervention and then following all three education sessions. The education sessions were carried out over a semester using a lunch and learn forum.Results: Our first assumption was that 50% of faculty would score below 70% on the pretest. Eligible nurse faculty 29/48 (60%) completed the GNCI© and scores show they had limited knowledge in three areas: nomenclature of genes and gene function, inheritance patterns, and the clinical application of genomics to human disease. Over half of nurse faculty 17/29 (59%) scored less than 70% on the GNCI© supporting our first assumption. The second assumption that over 85% of faculty would score at least 70% on the GNCI© after the education was not supported. The education sessions improved scores on the GNCI© in the 12/29 (41%) faculty who completed the measures prior to and after the intervention.Conclusion: Despite the growing knowledge about genomics/genetics and the application to clinical practice, health professionals like nurses are not competent in these concepts. Nursing faculty require competency in genomics and genetics in order to integrate these concepts in nursing curricula. Outcomes of this project show the need to provide education and support for nurse faculty in genomics and genetics. Keywords: education, genetics, genomics, incorporation, knowledge, undergraduate bachelors program