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This Week in Cell: Apr 6, 2016

University of California, Los Angeles, and Vanderbilt-Ingram Cancer Center researchers track the genomic and transcriptomic effects of immunotherapy-based treatment for metastatic melanoma in Cell. The team did whole-exome sequencing and/or RNA-sequencing on 38 metastatic melanoma tumors, before and after treatment with pembrolizumab or nivolumab — therapies designed to interfere with the PD-1 immune checkpoint blockade. When they compared features in tumors that did or did not respond to the immunotherapies, the researchers found that responsive tumors tended to contain BRCA2 gene mutations and/or high mutational loads, while 'innate anti-PD-1 resistance signature tumors' had enhanced expression of genes from cell adhesion, wound healing, and other pathways.

A pair of studies in Cell Press' American Journal of Human Genetics point to increased risk of non-syndromic cleft palate in individuals with alterations in the GRHL3 gene. For one of these, an international group led by investigators at the University of Pittsburgh did a genome-wide association study involving individuals from more than a dozen countries. The researchers uncovered suspicious SNPs when they compared genotypes for 78 with non-syndromic cleft palate, 1,700 unaffected controls, and 165 trios with affected children and unaffected parents. After replication analyses in nearly 2,000 more cases and controls, they focused in on a missense variant in GRHL3 that was linked to higher than usual prevalence of non-syndromic cleft palate in both the discovery and replication sets.

Researchers from Germany, Latvia, and the UK saw similar ties between GRHL3 and non-syndromic cleft palate when they sequenced coding regions of the gene in individuals with cleft lip and/or cleft palate. As they report in AJHG, that team sequenced GRHL3 exons in 96 European individual with non-syndromic cleft palate and 576 individuals with non-syndromic cleft lip (including some with both cleft lip and cleft palate). In those with cleft palate alone, the investigators saw enrichment for the same missense change to GRHL3 that was detected by the other team — results they verified through testing on additional non-syndromic cases and controls from Latvia and the UK. They also uncovered a handful of truncating mutations to GRHL3 in nine individuals with non-syndromic cleft palate.