regimens and larger sample sizes are necessary. Tumor-based assays require well-preserved biopsy material, are technically difficult, incur substantial costs, and have a slow turnaround time. By contrast, the MALDI-TOF-MS method that we have described can be performed using less than 1 l of pretreatment serum. Additionally, this method is inexpensive and rapid, and it can easily be fully automated. In our study, the assessment of EGFR gene mutation status using the serum proteomic classifier produced results that were not completely consistent with those obtained with ARMS in tumors. However, the inability to obtain primary tumor tissues, particularly through repeated biopsies, from patients with advanced-stage lung cancer makes the use of a serum proteomic classifier for analysis of EGFR gene mutation status clinically important given the high sensitivity of PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19703425 the technique and the favorable response to EGFR-TKIs in patients whose matched samples were labeled as “mutant” by the serum proteomic classifier. One limitation of our analysis is the inability of the serum proteomic classifier to precisely determine the type of EGFR gene TKI-sensitive mutation, such as exon 19 deletion and exon 21 mutation. Several studies have demonstrated that patients with an exon 19 deletion experienced, on average, longer PFS and OS than those with an L858R mutation after first-line EGFR-TKI treatment for advanced non-small cell lung cancer, indicating the clinical significance of the type of EGFR gene TKI-sensitive mutation. Therefore, our serum proteomic classifier must be modified to enable it to determine the type of EGFR gene TKI-sensitive mutation. Another limitation is the unknown biology underlying the correlation of these features with EGFR gene mutation status. Identification and analysis of the informative peaks might lead to important insights into the mechanisms underlying the correlation, and these studies are underway. In conclusion, in this study, we detected differences in serum peptides/proteins between patients with EGFR gene TKI-sensitive mutations and patients with wild-type EGFR genes; based on these differences, a classification algorithm was developed for the analysis of EGFR gene mutation status. Furthermore, EGFR gene mutation status, as determined by the serum proteomic classifier, may be predictive of the response to EGFR-TKIs. All of the above provide evidence to suggest that a serum proteomic classifier may be used instead of tumor tissue for analysis of EGFR gene mutation status in NSCLC. It will be important PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19705070 to validate these findings and determine the value of the assay in predicting patients’ responses to TKIs in randomized trials with larger cohorts. ~~ ~~ SB-1317 Resistance to inhibitors of cholinesterase 8 is a guanine nucleotide exchange factor for the subunits of heterotrimeric G proteins which was discovered during a genetic screen of C. elegans mutants that were defective in synaptic transmission. The RIC8 protein contains armadillo folding motifs, which are organized in a right-twisted -super helix. The functional studies have revealed that RIC8 
acts as a GEF for Gq, Gi, Go, G12, G13 but not Gs, which are activated by a paralogue of RIC8 . In contrast to G-protein coupled receptors, RIC8 interacts only with monomeric G subunit, participating in a non-canonic G-protein signaling pathway. RIC8 associates with G subunits in GDP form, triggering the release of GDP and enabling binding of GTP to G, which disrupts the complex, re