GNAS, GNAQ, and GNA11 alterations in patients with diverse cancers

Abstract

Background: Advances in deep sequencing technology have uncovered a widespread, protumorigenic role of guanine nucleotide-binding (G protein) α (GNA) subunits, particularly GNA subunits Gs (GNAS), Gq (GNAQ), and G11 (GNA11) (GNA*), in a diverse collection of malignancies. The objectives of the current study were: 1) to determine GNA* aberration status in a cohort of 1348 patients with cancer and 2) to examine tumor mutational burden, overall survival rates, and treatment outcomes in patients with GNA*-positive tumors versus those with tumors that had wild-type GNA*. Methods: For each patient, clinical and genomic data were collected from medical records. Next-generation sequencing was performed for each patient (range, 182-236 genes). Results: Aberrations of GNA* genes were identified in a subset of patients who had 8 of the 12 cancer types examined, and a significant association was observed for appendiceal cancer and ocular melanoma (P