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Jun Yang, Clinton Stewart and colleagues report the results of a genome-wide association study of cisplatin-induced ototoxicity among children undergoing treatment for brain tumors. They identify common variants in ACYP2 strongly associated with cisplatin-induced hearing loss and ototoxicity severity.
Trever Bivona and colleagues show that the Hippo pathway effector YAP promotes resistance to RAF and MEK inhibitor therapy in multiple types of BRAF-mutant tumors. The findings suggest that combined suppression of YAP and RAF-MEK signaling might enhance treatment response and prevent drug resistance.
Adam Shlien, Peter Campbell, Uri Tabori and colleagues report genome and exome sequencing of biallelic mismatch repair deficiency cancer samples from 12 children, including 10 high-grade gliomas. The hypermutational signature of the malignant glioma samples was consistent with a driver role for observed mutations in DNA polymerases ɛ or δ.
Furen Zhang and colleagues report the results of a three-stage genome-wide association study of leprosy in the Chinese population. They discover six new susceptibility loci and observe substantial overlap with loci previously implicated in autoimmune and inflammatory diseases.
Andrew Foote and colleagues report the whole-genome sequences and de novo assemblies of three marine mammal species—the walrus, killer whale and manatee—and an improved bottlenose dolphin genome. Their comparative genomic analysis finds evidence of parallel evolution across the marine mammal genomes.
Akiko Shimamura and colleagues report the identification of dominant-negative germline variants in ETV6 that cause thrombocytopenia and hematologic malignancies in the affected members of three families. All three mutations alter conserved amino acids in the transcriptional repressor encoded by ETV6 and affect its DNA binding.
Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.
Ding Ma, Hui Wang, Xun Xu and colleagues report a genome-wide map of HPV integration sites in cervical cancer samples and cell lines. In addition to discovering new integration hot spots, the authors identify microhomology-mediated DNA repair as a likely mechanism by which HPV integrates into the human genome.
John Rioux, Andre Franke, Tom Karlsen and colleagues perform a fine-mapping study of the HLA region in Crohn's disease and ulcerative colitis. They identify a primary role for HLA-DRB1*01:03 in both diseases and find evidence of heterozygous advantage in protection against ulcerative colitis.