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This Week in PNAS: Oct 9, 2018

In the early, online version of the Proceedings of the National Academy of Sciences, researchers from Genentech Oncology Biomarker Development, Yale Cancer Center, and elsewhere describe distinct contributions that PD-L1 expression in tumor- and tumor-infiltrating immune cell make to immunotherapy response in non-small cell lung cancer (NSCLC). The team characterized PD-L1 and other molecular features in tumor cells and tumor-infiltrating immune cells from 4,549 NSCLC cases before and after treatment with the anti-PD-L1 drug atezolizumab. Along with differences in PD-L1 expression, and mechanisms influencing it, in the immune and tumor compartments, the authors report that "PD-L1 on both cell types is important for predicting best response to atezulizumab in non-small cell lung cancer."

An Uppsala University team presents findings from an analysis of endogenous retrovirus (ERV) segregation in wild and domestic populations of the European rabbit, Oryctolagus cuniculus, sub-species cuniculus and algirus. The researchers searched for ERV insertions in whole-genome sequences for half a dozen domestic rabbit breeds, the rabbit reference genome, and 14 rabbit populations from southern France, the Iberian Peninsula, and Portugal's Porto Santo Island. "[W]e show that although ERV diversity tends to follow the host species' divergence, a subset of phylogenetically distinct retroviruses expanded along the rabbit host phylogeny," the authors write, noting that ERV standing variation "may be utilized to complement conventional comparative genomics strategies." 

A team led by investigators at Kaiser Permanente Northern California share results from a genome-wide association study focused on erectile dysfunction (ED). Based on genotype and self-reported ED survey data for 36,649 male participants in the Kaiser Permanente's Genetic Epidemiology Research in Adult Health and Aging cohort, the researchers identified five chromosome 6 SNPs with potential ties to ED. After a validation analysis in another 222,358 men from the UK Biobank study, they focused in on an ED-associated SNP called rs17185536 in an evolutionarily conserved region near the transcription factor-coding gene SIM1 for further analyses. GenomeWeb has more on the study, here

The Scan

Cancer Survival Linked to Mutational Burden in Pan-Cancer Analysis

A pan-cancer paper appearing in JCO Precision Oncology suggests tumor mutation patterns provide clues for predicting cancer survival that are independent of other prognostic factors.

Australian Survey Points to Public Support for Genetic Risk Disclosure in Relatives of At-Risk Individuals

A survey in the European Journal of Human Genetics suggests most adult Australians are in favor of finding out if a relative tests positive for a medically actionable genetic variant.

Study Links Evolution of Stony Coral Skeleton to Bicarbonate Transporter Gene

A PNAS paper focuses on a skeleton-related bicarbonate transporter gene introduced to stony coral ancestors by tandem duplication.

Hormone-Based Gene Therapy to Sterilize Domestic Cat

A new paper in Nature Communication suggests that gene therapy could be a safer alternative to spaying domestic cats.